The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases

Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis....

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Vydáno v:International journal of molecular sciences Ročník 21; číslo 24; s. 9739
Hlavní autoři: Cabral-Pacheco, Griselda A, Garza-Veloz, Idalia, Castruita-De la Rosa, Claudia, Ramirez-Acuña, Jesús M, Perez-Romero, Braulio A, Guerrero-Rodriguez, Jesús F, Martinez-Avila, Nadia, Martinez-Fierro, Margarita L
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI 20.12.2020
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ISSN:1422-0067, 1422-0067
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Abstract Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.
AbstractList Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.
Author Ramirez-Acuña, Jesús M
Guerrero-Rodriguez, Jesús F
Martinez-Avila, Nadia
Garza-Veloz, Idalia
Martinez-Fierro, Margarita L
Cabral-Pacheco, Griselda A
Perez-Romero, Braulio A
Castruita-De la Rosa, Claudia
AuthorAffiliation Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico; gris_elda_ai91@hotmail.com (G.AC.-P.); castruitade@gmail.com (C.C.-D.l.R.); jesusm.ra94@gmail.com (J.MR.-A.); alekhandroperes@gmail.com (B.AP.-R.); guerreroajf@gmail.com (J.FG.-R.); ik.otik88@gmail.com (N.M.-A.)
AuthorAffiliation_xml – name: Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico; gris_elda_ai91@hotmail.com (G.AC.-P.); castruitade@gmail.com (C.C.-D.l.R.); jesusm.ra94@gmail.com (J.MR.-A.); alekhandroperes@gmail.com (B.AP.-R.); guerreroajf@gmail.com (J.FG.-R.); ik.otik88@gmail.com (N.M.-A.)
Author_xml – sequence: 1
  givenname: Griselda A
  surname: Cabral-Pacheco
  fullname: Cabral-Pacheco, Griselda A
– sequence: 2
  givenname: Idalia
  orcidid: 0000-0002-6307-1696
  surname: Garza-Veloz
  fullname: Garza-Veloz, Idalia
– sequence: 3
  givenname: Claudia
  surname: Castruita-De la Rosa
  fullname: Castruita-De la Rosa, Claudia
– sequence: 4
  givenname: Jesús M
  orcidid: 0000-0002-9183-2034
  surname: Ramirez-Acuña
  fullname: Ramirez-Acuña, Jesús M
– sequence: 5
  givenname: Braulio A
  surname: Perez-Romero
  fullname: Perez-Romero, Braulio A
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  givenname: Jesús F
  surname: Guerrero-Rodriguez
  fullname: Guerrero-Rodriguez, Jesús F
– sequence: 7
  givenname: Nadia
  surname: Martinez-Avila
  fullname: Martinez-Avila, Nadia
– sequence: 8
  givenname: Margarita L
  orcidid: 0000-0003-1478-9068
  surname: Martinez-Fierro
  fullname: Martinez-Fierro, Margarita L
BackLink https://www.ncbi.nlm.nih.gov/pubmed/33419373$$D View this record in MEDLINE/PubMed
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metalloproteinase inhibitors
human diseases
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Snippet Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost...
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StartPage 9739
SubjectTerms Chronic Disease - prevention & control
Diabetes Mellitus - genetics
Diabetes Mellitus - pathology
Extracellular Matrix - genetics
Humans
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 9 - genetics
Matrix Metalloproteinases - genetics
Neovascularization, Physiologic - genetics
Review
Tissue Inhibitor of Metalloproteinase-1 - genetics
Tissue Inhibitor of Metalloproteinase-3
Tissue Inhibitor of Metalloproteinases - genetics
Title The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases
URI https://www.ncbi.nlm.nih.gov/pubmed/33419373
https://www.proquest.com/docview/2476561548
https://pubmed.ncbi.nlm.nih.gov/PMC7767220
Volume 21
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