TGF-β1 modulates podocyte migration by regulating the expression of integrin-β1 and -β3 through different signaling pathways - 11/07/18
, Jer-Ming Chang c, Eddy-Essen Chang d, Hung-Chun Chen d, Yu-Lin Yang eBienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
TGF-β1 inhibits integrin-β1 maturation through MAP kinases pathway, but increases integrin-β3 expression through Smad2/3 and MAP kinases pathways in podocytes. The increased integrin-β3 promotes podocyte adhesion and migration that may lead to foot process effacement.
Highlights |
• | TGF-β1 and integrins regulate podocyte migration that can lead to foot process effacement, proteinuria and glomerulopathy. |
• | TGF-β1 down-regulates the maturation of integrin-β1 and up-regulates the integrin-β3 through different pathways. |
• | The increase in integrin-β3 expression promotes podocyte migration and adhesion. |
• | This study identifies a novel mechanism for TGF-β1 signaling in regulating podocytes adhesion and migration. |
Abstract |
Aims |
Podocyte migration may lead foot process effacement and proteinuria. Transforming growth factor-β1 (TGF-β1) and integrins are involved in the adhesion and migration of cells. However, the crosstalk of TGF-β1 and integrins is unclear. Here, we examined how TGF-β1 regulates the expression of integrin-β1 and -β3 to modulate podocyte adhesion and migration.
Main methods |
Podocytes were exposed to TGF-β1 and/or the inhibitors of Smad2/3, ERK and p38, then the expression of integrin-β1 and -β3 was assessed by Real-time PCR and western blot analyses. Podocyte adhesion and migration were measured under TGF-β1 treatment and/or anti-integrin-β3 antibody by cell adhesion assay and wound healing assay.
Key findings |
TGF-β1 had no effect on integrin-β1 mRNA expression. In the analysis of protein expression, TGF-β1 decreased the mature form of integrin-β1, but increased both the precursor form and core peptide of integrin-β1. The inhibitors of ERK and p38, but not Smad2/3, abrogated TGF-β1-induced changes in integrin-β1 protein expression. TGF-β1 increased integrin-β3 mRNA and protein levels. The inhibitors of Smad2/3, ERK and p38 attenuated the TGF-β1-induced increase in integrin-β3 mRNA and protein levels. Podocyte adhesion and migration were enhanced under the stimulation of TGF-β1. The blockade of interactions between integrin-αvβ3 and the extracellular matrix by the anti-integrin-β3 antibody abrogated the TGF-β1-induced enhancement in podocyte adhesion and migration.
Significance |
Our results demonstrate that TGF-β1up-regulates integrin-β3 expression and down-regulates integrin-β1 expression through different pathways. The up-regulation of integrin-β3 expression enhances podocyte migration. This study provides a novel mechanism for TGF-β1 signaling in regulating podocyte migration.
Le texte complet de cet article est disponible en PDF.Keywords : Adhesion, Integrins, Migration, Podocytes
Plan
Vol 105
P. 974-980 - septembre 2018 Retour au numéro
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