Mechanisms of pathological scarring: Role of myofibroblasts and current developments

ABSTRACT Myofibroblasts play a key role in the wound‐healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation....

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Vydané v:Wound repair and regeneration Ročník 19; číslo s1; s. s10 - s15
Hlavní autori: Sarrazy, Vincent, Billet, Fabrice, Micallef, Ludovic, Coulomb, Bernard, Desmoulière, Alexis
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Malden, USA Blackwell Publishing Inc 01.09.2011
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ISSN:1067-1927, 1524-475X, 1524-475X
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Abstract ABSTRACT Myofibroblasts play a key role in the wound‐healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibroblast differentiation and apoptosis are both modulated by cytokines, mechanical stress, and, more generally, cell–cell and cell–matrix interactions. Tissue repair allows tissues and organs to recover, at least partially, functional properties that have been lost through trauma or disease. Embryonic skin wounds are repaired without scarring or fibrosis, whereas skin wound repair in adults always leads to scar formation, which may have functional or esthetic consequences, as in the case of hypertrophic scars, for example. Skin wound repair involves a precise remodeling process, particularly in the dermal compartment, during which fibroblasts/myofibroblasts play a central role. This article reviews the origins of myofibroblasts and their role in normal and pathological skin wound healing. This article focuses on traumatic skin wound healing, but largely, the same mechanisms apply in other physiological and pathological settings. Tissue healing in other organs is examined by comparison, as well as the stromal reaction associated with cancer. New approaches to wound/scar therapy are discussed.
AbstractList Myofibroblasts play a key role in the wound-healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibroblast differentiation and apoptosis are both modulated by cytokines, mechanical stress, and, more generally, cell-cell and cell-matrix interactions. Tissue repair allows tissues and organs to recover, at least partially, functional properties that have been lost through trauma or disease. Embryonic skin wounds are repaired without scarring or fibrosis, whereas skin wound repair in adults always leads to scar formation, which may have functional or esthetic consequences, as in the case of hypertrophic scars, for example. Skin wound repair involves a precise remodeling process, particularly in the dermal compartment, during which fibroblasts/myofibroblasts play a central role. This article reviews the origins of myofibroblasts and their role in normal and pathological skin wound healing. This article focuses on traumatic skin wound healing, but largely, the same mechanisms apply in other physiological and pathological settings. Tissue healing in other organs is examined by comparison, as well as the stromal reaction associated with cancer. New approaches to wound/scar therapy are discussed.Myofibroblasts play a key role in the wound-healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibroblast differentiation and apoptosis are both modulated by cytokines, mechanical stress, and, more generally, cell-cell and cell-matrix interactions. Tissue repair allows tissues and organs to recover, at least partially, functional properties that have been lost through trauma or disease. Embryonic skin wounds are repaired without scarring or fibrosis, whereas skin wound repair in adults always leads to scar formation, which may have functional or esthetic consequences, as in the case of hypertrophic scars, for example. Skin wound repair involves a precise remodeling process, particularly in the dermal compartment, during which fibroblasts/myofibroblasts play a central role. This article reviews the origins of myofibroblasts and their role in normal and pathological skin wound healing. This article focuses on traumatic skin wound healing, but largely, the same mechanisms apply in other physiological and pathological settings. Tissue healing in other organs is examined by comparison, as well as the stromal reaction associated with cancer. New approaches to wound/scar therapy are discussed.
ABSTRACT Myofibroblasts play a key role in the wound‐healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibroblast differentiation and apoptosis are both modulated by cytokines, mechanical stress, and, more generally, cell–cell and cell–matrix interactions. Tissue repair allows tissues and organs to recover, at least partially, functional properties that have been lost through trauma or disease. Embryonic skin wounds are repaired without scarring or fibrosis, whereas skin wound repair in adults always leads to scar formation, which may have functional or esthetic consequences, as in the case of hypertrophic scars, for example. Skin wound repair involves a precise remodeling process, particularly in the dermal compartment, during which fibroblasts/myofibroblasts play a central role. This article reviews the origins of myofibroblasts and their role in normal and pathological skin wound healing. This article focuses on traumatic skin wound healing, but largely, the same mechanisms apply in other physiological and pathological settings. Tissue healing in other organs is examined by comparison, as well as the stromal reaction associated with cancer. New approaches to wound/scar therapy are discussed.
Myofibroblasts play a key role in the wound‐healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibroblast differentiation and apoptosis are both modulated by cytokines, mechanical stress, and, more generally, cell–cell and cell–matrix interactions. Tissue repair allows tissues and organs to recover, at least partially, functional properties that have been lost through trauma or disease. Embryonic skin wounds are repaired without scarring or fibrosis, whereas skin wound repair in adults always leads to scar formation, which may have functional or esthetic consequences, as in the case of hypertrophic scars, for example. Skin wound repair involves a precise remodeling process, particularly in the dermal compartment, during which fibroblasts/myofibroblasts play a central role. This article reviews the origins of myofibroblasts and their role in normal and pathological skin wound healing. This article focuses on traumatic skin wound healing, but largely, the same mechanisms apply in other physiological and pathological settings. Tissue healing in other organs is examined by comparison, as well as the stromal reaction associated with cancer. New approaches to wound/scar therapy are discussed.
Author Coulomb, Bernard
Micallef, Ludovic
Sarrazy, Vincent
Desmoulière, Alexis
Billet, Fabrice
Author_xml – sequence: 1
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  surname: Sarrazy
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  givenname: Fabrice
  surname: Billet
  fullname: Billet, Fabrice
  organization: EA 3842 and Département de Physiologie, Institut Fédératif de Recherche 145, Faculté de Pharmacie, Université de Limoges, Limoges, France
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  givenname: Ludovic
  surname: Micallef
  fullname: Micallef, Ludovic
  organization: EA 3842 and Département de Physiologie, Institut Fédératif de Recherche 145, Faculté de Pharmacie, Université de Limoges, Limoges, France
– sequence: 4
  givenname: Bernard
  surname: Coulomb
  fullname: Coulomb, Bernard
  organization: Inserm U970, Réparation Artérielle, Université Paris Descartes, Paris, France
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  givenname: Alexis
  surname: Desmoulière
  fullname: Desmoulière, Alexis
  organization: EA 3842 and Département de Physiologie, Institut Fédératif de Recherche 145, Faculté de Pharmacie, Université de Limoges, Limoges, France
BackLink https://www.ncbi.nlm.nih.gov/pubmed/21793960$$D View this record in MEDLINE/PubMed
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PublicationCentury 2000
PublicationDate September/October 2011
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  text: September/October 2011
PublicationDecade 2010
PublicationPlace Malden, USA
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PublicationTitle Wound repair and regeneration
PublicationTitleAlternate Wound Repair Regen
PublicationYear 2011
Publisher Blackwell Publishing Inc
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References Desmoulière A, Redard M, Darby IA, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 1995; 146: 55-66.
Ng CP, Hinz B, Swartz MA. Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro. J Cell Sci 2005; 118: 4731-9.
Verhaegen PDHM, van Zuijlen PPM, Pennings NM, van Marle J, Niessen FB, van der Horst CMAM, Middelkoop E. Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: an objective histopathological analysis. Wound Rep Regen 2009; 17: 649-56.
Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 1993; 122: 103-11.
Yang L, Scott PG, Dodd C, Medina A, Jiao H, Shankowsky HA, Ghahary A, Tredget EE. Identification of fibrocytes in postburn hypertrophic scar. Wound Rep Regen 2005; 13: 398-404.
Opalenik SR, Davidson JM. Fibroblast differentiation of bone marrow-derived cells during wound repair. FASEB J 2005; 19: 1561-3.
Gallant-Behm CL, Mustoe TA. Occlusion regulates epidermal cytokine production and inhibits scar formation. Wound Rep Regen 2010; 18: 235-44.
Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol 2007; 127: 998-1008.
Bellemare J, Roberge CJ, Bergeron D, Lopez-Vallé CA, Roy M, Moulin VJ. Epidermis promotes dermal fibrosis: role in the pathogenesis of hypertrophic scars. J Pathol 2005; 206: 1-8.
Noël A, Jost M, Maquoi E. Matrix metalloproteinases at cancer tumor-host interface. Semin Cell Dev Biol 2008; 19: 52-60.
Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 2004; 64: 8492-5.
Kohan M, Muro AF, White ES, Berkman N. EDA-containing cellular fibronectin induces fibroblast differentiation through binding to α4β7 integrin receptor and MAPK/Erk 1/2-dependent signaling. FASEB J 2010; 24: 4503-12.
Schäfer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 2008; 9: 628-38.
Forbes SJ, Russo FP, Rey V, Burra P, Rugge M, Wright NA, Alison MR. A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology 2004; 126: 955-63.
Higashiyama R, Nakao S, Shibusawa Y, Ishikawa O, Moro T, Mikami K, Fukumitsu H, Ueda Y, Minakawa K, Tabata Y, Bou-Gharios G, Inagaki Y. Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice. J Invest Dermatol 2011; 131: 529-36.
Wells RG. The role of matrix stiffness in regulating cell behavior. Hepatology 2008; 47: 1394-400.
Lataillade JJ, Doucet C, Bey E, Carsin H, Huet C, Clairand I, Bottollier-Depois JF, Chapel A, Ernou I, Gourven M, Boutin L, Hayden A, Carcamo C, Buglova E, Joussemet M, de Revel T, Gourmelon P. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med 2007; 2: 785-94.
Rajkumar VS, Howell K, Csiszar K, Denton CP, Black CM, Abraham DJ. Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis. Arthritis Res Ther 2005; 7: R1113-23.
Radisky DC, Kenny PA, Bissell MJ. Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 2007; 101: 830-9.
Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 2001; 166: 7556-62.
Hakvoort TE, Altun V, Ramrattan RS, van der Kwast TH, Benner R, van Zuijlen PP, Vloemans AF, Prens EP. Epidermal participation in post-burn hypertrophic scar development. Virchows Arch 1999; 434: 221-6.
Le Blanc K, Ringdén O. Mesenchymal stem cells: properties and role in clinical bone marrow transplantation. Curr Opin Immunol 2006; 18: 586-91.
Hattori N, Mochizuki S, Kishi K, Nakajima T, Takaishi H, D'Armiento J, Okada Y. MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing. Am J Pathol 2009; 175: 533-46.
Hinz B, Gabbiani G. Mechanisms of force generation and transmission by myofibroblasts. Curr Opin Biotechnol 2003; 14: 538-46.
Jahoda C, Reynolds A. Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet 2001; 358: 1445-8.
Akaishi S, Ogawa R, Hyakusoku H. Keloid and hypertrophic scar: neurogenic inflammation hypotheses. Med Hypotheses 2008; 71: 32-8.
Costa AMA, Peyrol S, Porto LC, Comparin JP, Foyatier JL, Desmoulière A. Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scars. Am J Pathol 1999; 155: 1671-9.
Lee JY, Yang CC, Chao SC, Wong TW. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathol 2004; 26: 379-84.
Guyot C, Lepreux S, Combe C, Doudnikoff E, Bioulac-Sage P, Balabaud C, Desmoulière A. Hepatic fibrosis and cirrhosis: the (myo)fibroblastic cell subpopulations involved. Int J Biochem Cell Biol 2006; 38: 135-51.
Hinz B. The myofibroblast: paradigm for a mechanically active cell. J Biomech 2010; 43: 146-55.
Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-b1. J Cell Biol 1998; 142: 873-81.
Ishii G, Sangai T, Oda T, Aoyagi Y, Hasebe T, Kanomata N, Endoh Y, Okumura C, Okuhara Y, Magae J, Emura M, Ochiva T, Ochiai A. Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun 2003; 309: 232-40.
Sugimoto H, Mundel TM, Kieran MW, Kalluri R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 2006; 5: 1640-6.
Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5: 146-56.
Rajkumar VS, Shiwen X, Bostrom M, Leoni P, Muddle J, Ivarsson M, Gerdin B, Denton CP, Bou-Gharios G, Black CM, Abraham DJ. Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. Am J Pathol 2006; 169: 2254-65.
Hinz B, Gabbiani G, Chaponnier C. The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. J Cell Biol 2002; 157: 657-63.
Aarabi S, Bhatt KA, Shi Y, Paterno J, Chang EI, Loh SA, Holmes JW, Longaker MT, Yee H, Gurtner GC. Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J 2007; 21: 3250-61.
De Wever O, Demetter P, Mareel M, Bracke M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer 2008; 123: 2229-38.
Orimo A, Weinberg RA. Heterogeneity of stromal fibroblasts in tumors. Cancer Biol Ther 2007; 6: 618-9.
Dabiri G, Tumbarello DA, Turner CE, Van de Water L. Hic-5 promotes the hypertrophic scar myofibroblast phenotype by regulating the TGF-beta1 autocrine loop. J Invest Dermatol 2008; 128: 2518-25.
Potenta S, Zeisberg E, Kalluri R. The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer 2008; 99: 1375-9.
Darby IA, Bisucci T, Pittet B, Garbin S, Gabbiani G, Desmoulière A. Skin flap induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression. J Pathol 2002; 197: 117-27.
Hinz B, Mastrangelo D, Iselin CE, Chaponnier C, Gabbiani G. Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol 2001; 159: 1009-20.
Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008; 453: 314-21.
Ehrlich HP, Desmoulière A, Diegelmann RF, Cohen IK, Compton CC, Garner WL, Kapanci Y, Gabbiani G. Morphological and immunochemical differences between keloid and hypertrophic scar. Am J Pathol 1994; 145: 105-13.
van den Bogaerdt AJ, van der Veen VC, van Zuijlen PPM, Reijnen L, Verkerk M, Bank RA, Middelkoop E, Ulrich MMW. Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells: are mesenchymal stromal cells involved in scar formation? Wound Rep Regen 2009; 17: 548-58.
Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003; 83: 835-70.
Ulrich MMW, Verkerk M, Reijnen L, Vlig M, van den Bogaerdt AJ, Middelkoop E. Expression profile of proteins involved in scar formation in the healing process of full-thickness excisional wounds in the porcine model. Wound Rep Regen 2007; 15: 482-90.
Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci 2008; 13: 3532-48.
Xi-Qiao W, Ying-Kai L, Chun Q, Shu-Liang L. Hyperactivity of fibroblasts and functional regression of endothelial cells contribute to microvessel occlusion in hypertrophic scarring. Microvasc Res 2009; 77: 204-11.
Sorrell JM, Caplan AI. Fibroblast heterogeneity: more than skin deep. J Cell Sci 2004; 117: 667-75.
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References_xml – reference: Kohan M, Muro AF, White ES, Berkman N. EDA-containing cellular fibronectin induces fibroblast differentiation through binding to α4β7 integrin receptor and MAPK/Erk 1/2-dependent signaling. FASEB J 2010; 24: 4503-12.
– reference: Sugimoto H, Mundel TM, Kieran MW, Kalluri R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol Ther 2006; 5: 1640-6.
– reference: Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-b1. J Cell Biol 1998; 142: 873-81.
– reference: Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol 2007; 127: 998-1008.
– reference: Jahoda C, Reynolds A. Hair follicle dermal sheath cells: unsung participants in wound healing. Lancet 2001; 358: 1445-8.
– reference: van den Bogaerdt AJ, van der Veen VC, van Zuijlen PPM, Reijnen L, Verkerk M, Bank RA, Middelkoop E, Ulrich MMW. Collagen cross-linking by adipose-derived mesenchymal stromal cells and scar-derived mesenchymal cells: are mesenchymal stromal cells involved in scar formation? Wound Rep Regen 2009; 17: 548-58.
– reference: Verhaegen PDHM, van Zuijlen PPM, Pennings NM, van Marle J, Niessen FB, van der Horst CMAM, Middelkoop E. Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: an objective histopathological analysis. Wound Rep Regen 2009; 17: 649-56.
– reference: Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res 2004; 64: 8492-5.
– reference: Hinz B, Mastrangelo D, Iselin CE, Chaponnier C, Gabbiani G. Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol 2001; 159: 1009-20.
– reference: Ishii G, Sangai T, Oda T, Aoyagi Y, Hasebe T, Kanomata N, Endoh Y, Okumura C, Okuhara Y, Magae J, Emura M, Ochiva T, Ochiai A. Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun 2003; 309: 232-40.
– reference: Aarabi S, Bhatt KA, Shi Y, Paterno J, Chang EI, Loh SA, Holmes JW, Longaker MT, Yee H, Gurtner GC. Mechanical load initiates hypertrophic scar formation through decreased cellular apoptosis. FASEB J 2007; 21: 3250-61.
– reference: Sorrell JM, Caplan AI. Fibroblast heterogeneity: more than skin deep. J Cell Sci 2004; 117: 667-75.
– reference: Ng CP, Hinz B, Swartz MA. Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro. J Cell Sci 2005; 118: 4731-9.
– reference: Higashiyama R, Nakao S, Shibusawa Y, Ishikawa O, Moro T, Mikami K, Fukumitsu H, Ueda Y, Minakawa K, Tabata Y, Bou-Gharios G, Inagaki Y. Differential contribution of dermal resident and bone marrow-derived cells to collagen production during wound healing and fibrogenesis in mice. J Invest Dermatol 2011; 131: 529-36.
– reference: Darby IA, Bisucci T, Pittet B, Garbin S, Gabbiani G, Desmoulière A. Skin flap induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression. J Pathol 2002; 197: 117-27.
– reference: Ehrlich HP, Desmoulière A, Diegelmann RF, Cohen IK, Compton CC, Garner WL, Kapanci Y, Gabbiani G. Morphological and immunochemical differences between keloid and hypertrophic scar. Am J Pathol 1994; 145: 105-13.
– reference: Hinz B, Gabbiani G. Mechanisms of force generation and transmission by myofibroblasts. Curr Opin Biotechnol 2003; 14: 538-46.
– reference: Dabiri G, Tumbarello DA, Turner CE, Van de Water L. Hic-5 promotes the hypertrophic scar myofibroblast phenotype by regulating the TGF-beta1 autocrine loop. J Invest Dermatol 2008; 128: 2518-25.
– reference: Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5: 146-56.
– reference: Hinz B. The myofibroblast: paradigm for a mechanically active cell. J Biomech 2010; 43: 146-55.
– reference: De Wever O, Demetter P, Mareel M, Bracke M. Stromal myofibroblasts are drivers of invasive cancer growth. Int J Cancer 2008; 123: 2229-38.
– reference: Bellemare J, Roberge CJ, Bergeron D, Lopez-Vallé CA, Roy M, Moulin VJ. Epidermis promotes dermal fibrosis: role in the pathogenesis of hypertrophic scars. J Pathol 2005; 206: 1-8.
– reference: Rajkumar VS, Howell K, Csiszar K, Denton CP, Black CM, Abraham DJ. Shared expression of phenotypic markers in systemic sclerosis indicates a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis. Arthritis Res Ther 2005; 7: R1113-23.
– reference: Xi-Qiao W, Ying-Kai L, Chun Q, Shu-Liang L. Hyperactivity of fibroblasts and functional regression of endothelial cells contribute to microvessel occlusion in hypertrophic scarring. Microvasc Res 2009; 77: 204-11.
– reference: Radisky DC, Kenny PA, Bissell MJ. Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT? J Cell Biochem 2007; 101: 830-9.
– reference: Rajkumar VS, Shiwen X, Bostrom M, Leoni P, Muddle J, Ivarsson M, Gerdin B, Denton CP, Bou-Gharios G, Black CM, Abraham DJ. Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. Am J Pathol 2006; 169: 2254-65.
– reference: Opalenik SR, Davidson JM. Fibroblast differentiation of bone marrow-derived cells during wound repair. FASEB J 2005; 19: 1561-3.
– reference: Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci 2008; 13: 3532-48.
– reference: Guyot C, Lepreux S, Combe C, Doudnikoff E, Bioulac-Sage P, Balabaud C, Desmoulière A. Hepatic fibrosis and cirrhosis: the (myo)fibroblastic cell subpopulations involved. Int J Biochem Cell Biol 2006; 38: 135-51.
– reference: Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 2001; 166: 7556-62.
– reference: Costa AMA, Peyrol S, Porto LC, Comparin JP, Foyatier JL, Desmoulière A. Mechanical forces induce scar remodeling. Study in non-pressure-treated versus pressure-treated hypertrophic scars. Am J Pathol 1999; 155: 1671-9.
– reference: Lee JY, Yang CC, Chao SC, Wong TW. Histopathological differential diagnosis of keloid and hypertrophic scar. Am J Dermatopathol 2004; 26: 379-84.
– reference: Hattori N, Mochizuki S, Kishi K, Nakajima T, Takaishi H, D'Armiento J, Okada Y. MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing. Am J Pathol 2009; 175: 533-46.
– reference: Forbes SJ, Russo FP, Rey V, Burra P, Rugge M, Wright NA, Alison MR. A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology 2004; 126: 955-63.
– reference: Lataillade JJ, Doucet C, Bey E, Carsin H, Huet C, Clairand I, Bottollier-Depois JF, Chapel A, Ernou I, Gourven M, Boutin L, Hayden A, Carcamo C, Buglova E, Joussemet M, de Revel T, Gourmelon P. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy. Regen Med 2007; 2: 785-94.
– reference: Ulrich MMW, Verkerk M, Reijnen L, Vlig M, van den Bogaerdt AJ, Middelkoop E. Expression profile of proteins involved in scar formation in the healing process of full-thickness excisional wounds in the porcine model. Wound Rep Regen 2007; 15: 482-90.
– reference: Akaishi S, Ogawa R, Hyakusoku H. Keloid and hypertrophic scar: neurogenic inflammation hypotheses. Med Hypotheses 2008; 71: 32-8.
– reference: Potenta S, Zeisberg E, Kalluri R. The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer 2008; 99: 1375-9.
– reference: Gallant-Behm CL, Mustoe TA. Occlusion regulates epidermal cytokine production and inhibits scar formation. Wound Rep Regen 2010; 18: 235-44.
– reference: Wells RG. The role of matrix stiffness in regulating cell behavior. Hepatology 2008; 47: 1394-400.
– reference: Hakvoort TE, Altun V, Ramrattan RS, van der Kwast TH, Benner R, van Zuijlen PP, Vloemans AF, Prens EP. Epidermal participation in post-burn hypertrophic scar development. Virchows Arch 1999; 434: 221-6.
– reference: Schäfer M, Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 2008; 9: 628-38.
– reference: Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008; 453: 314-21.
– reference: Noël A, Jost M, Maquoi E. Matrix metalloproteinases at cancer tumor-host interface. Semin Cell Dev Biol 2008; 19: 52-60.
– reference: Hinz B, Gabbiani G, Chaponnier C. The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. J Cell Biol 2002; 157: 657-63.
– reference: Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 1993; 122: 103-11.
– reference: Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 2003; 83: 835-70.
– reference: Yang L, Scott PG, Dodd C, Medina A, Jiao H, Shankowsky HA, Ghahary A, Tredget EE. Identification of fibrocytes in postburn hypertrophic scar. Wound Rep Regen 2005; 13: 398-404.
– reference: Desmoulière A, Redard M, Darby IA, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol 1995; 146: 55-66.
– reference: Le Blanc K, Ringdén O. Mesenchymal stem cells: properties and role in clinical bone marrow transplantation. Curr Opin Immunol 2006; 18: 586-91.
– reference: Orimo A, Weinberg RA. Heterogeneity of stromal fibroblasts in tumors. Cancer Biol Ther 2007; 6: 618-9.
– volume: 197
  start-page: 117
  year: 2002
  end-page: 27
  article-title: Skin flap induced regression of granulation tissue correlates with reduced growth factor and increased metalloproteinase expression
  publication-title: J Pathol
– volume: 47
  start-page: 1394
  year: 2008
  end-page: 400
  article-title: The role of matrix stiffness in regulating cell behavior
  publication-title: Hepatology
– volume: 17
  start-page: 649
  year: 2009
  end-page: 56
  article-title: Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin
  publication-title: an objective histopathological analysis
– volume: 453
  start-page: 314
  year: 2008
  end-page: 21
  article-title: Wound repair and regeneration
  publication-title: Nature
– volume: 17
  start-page: 548
  year: 2009
  end-page: 58
  article-title: Collagen cross‐linking by adipose‐derived mesenchymal stromal cells and scar‐derived mesenchymal cells
  publication-title: are mesenchymal stromal cells involved in scar formation?
– volume: 26
  start-page: 379
  year: 2004
  end-page: 84
  article-title: Histopathological differential diagnosis of keloid and hypertrophic scar
  publication-title: Am J Dermatopathol
– volume: 99
  start-page: 1375
  year: 2008
  end-page: 9
  article-title: The role of endothelial‐to‐mesenchymal transition in cancer progression
  publication-title: Br J Cancer
– volume: 145
  start-page: 105
  year: 1994
  end-page: 13
  article-title: Morphological and immunochemical differences between keloid and hypertrophic scar
  publication-title: Am J Pathol
– volume: 126
  start-page: 955
  year: 2004
  end-page: 63
  article-title: A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis
  publication-title: Gastroenterology
– volume: 15
  start-page: 482
  year: 2007
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Snippet ABSTRACT Myofibroblasts play a key role in the wound‐healing process, promoting wound closure and matrix deposition. These cells normally disappear from...
Myofibroblasts play a key role in the wound‐healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation...
Myofibroblasts play a key role in the wound-healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation...
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SubjectTerms Cicatrix - physiopathology
Cicatrix, Hypertrophic - physiopathology
Granulation Tissue - physiology
Humans
Keloid - physiopathology
Liver - physiopathology
Myofibroblasts - cytology
Myofibroblasts - physiology
Neoplasms - physiopathology
Stress, Mechanical
Transforming Growth Factor beta1 - physiology
Wound Healing - physiology
Title Mechanisms of pathological scarring: Role of myofibroblasts and current developments
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https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1524-475X.2011.00708.x
https://www.ncbi.nlm.nih.gov/pubmed/21793960
https://www.proquest.com/docview/1780505447
https://www.proquest.com/docview/881001135
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