TGFβ1-Smad canonical and -Erk noncanonical pathways participate in interleukin-17-induced epithelial–mesenchymal transition in Sjögren’s syndrome

Interleukin-17 (IL-17) is a pleiotropic cytokine that plays a primary role in triggering epithelial–mesenchymal transition (EMT) in many chronic inflammatory diseases. EMT plays a critical role in the progression of salivary gland (SG) fibrosis in primary Sjögren’s syndrome (pSS). This study focused...

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Vydáno v:Laboratory investigation Ročník 100; číslo 6; s. 824 - 836
Hlavní autoři: Sisto, Margherita, Lorusso, Loredana, Ingravallo, Giuseppe, Ribatti, Domenico, Lisi, Sabrina
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Nature Publishing Group US 01.06.2020
Nature Publishing Group
Témata:
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Activation
Activation analysis
Aged
Cells, Cultured
Cytokines
Enzyme inhibitors
Epithelial cells
Epithelial-Mesenchymal Transition - physiology
Extracellular signal-regulated kinase
Fibrosis
Humans
Inflammatory diseases
Interleukin 17
Interleukin-17 - metabolism
Interleukins
Kinases
Laboratory Medicine
Lip - cytology
MAP Kinase Signaling System - physiology
Medicine
Medicine & Public Health
Mesenchyme
Middle Aged
Pathology
Salivary gland
Salivary glands
Signal transduction
Sjogren's syndrome
Sjogren's Syndrome - metabolism
Sjogren's Syndrome - pathology
Smad protein
Smad Proteins - metabolism
Smad2 protein
Transforming Growth Factor beta1 - metabolism
Transforming growth factor-b1
ISSN:0023-6837, 1530-0307, 1530-0307
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Shrnutí:Interleukin-17 (IL-17) is a pleiotropic cytokine that plays a primary role in triggering epithelial–mesenchymal transition (EMT) in many chronic inflammatory diseases. EMT plays a critical role in the progression of salivary gland (SG) fibrosis in primary Sjögren’s syndrome (pSS). This study focused on the activation of the canonical TGF-β1/Smad2/3 and noncanonical TGF-β1/Erk1/2 pathways in IL-17-dependent TGFβ1-induced EMT in human SG epithelial cells (SGEC) derived from healthy subjects. The expression of phosphorylated Smad2/3 and Erk1/2 during IL-17 treatment-stimulated EMT was evaluated in healthy SGEC. Cotreatment with IL-17 and specific TGFβ receptor type I kinase inhibitor SB431542, or Erk 1/2 inhibitor U0126, abrogates the corresponding morphological changes and EMT phenotypic markers expression in healthy SGEC. Interestingly, inhibition of canonical TGFβ1/Smad2/3 signal transduction had no effect on activation of the noncanonical TGFβ1/Erk1/2/EMT pathway, suggesting that the two pathways act independently in activating IL-17-dependent EMT in SGEC. Epithelial–mesenchymal transition (EMT) plays a critical role in the progression of salivary gland (SG) fibrosis in primary Sjögren’s syndrome. This study demonstrates the IL-17-dependent activation of EMT in human SG epithelial cells that occurs through both the canonical TGF-β1/Smad2/3 and noncanonical TGF-β1/Erk1/2 pathways.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0023-6837
1530-0307
1530-0307
DOI:10.1038/s41374-020-0373-z