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The Stiffness of Cardiac Fibroblast Substrates Exerts a Regulatory Influence on Collagen Metabolism via α2β1 Integrin, FAK and Src Kinases

Information about mechanical strain in the extracellular space is conducted along collagen fibers connected with integrins and then transmitted within cells. An aim of the study is to verify the hypothesis that the stiffness of cardiac human fibroblast substrates exerts a regulatory effect on collag...

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Published in:Cells (Basel, Switzerland) Switzerland), 2021-12, Vol.10 (12), p.3506
Main Authors: Gałdyszyńska, Małgorzata, Radwańska, Paulina, Szymański, Jacek, Drobnik, Jacek
Format: Article
Language:English
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Summary:Information about mechanical strain in the extracellular space is conducted along collagen fibers connected with integrins and then transmitted within cells. An aim of the study is to verify the hypothesis that the stiffness of cardiac human fibroblast substrates exerts a regulatory effect on collagen metabolism via integrin α2β1 and downstream signaling. The experiments were performed on human cardiac fibroblasts cultured on stiff or soft polyacrylamide gels. Extracellular and intracellular collagen content, metalloproteinase-1 (MMP-1), metalloproteinase-9 (MMP-9) and expression of the α1 chain of the procollagen type I gene ( ) were elevated in cultures settled on soft substrate. The substrate stiffness did not modify tissue inhibitors of matrix metalloproteinase capacity (TIMPs 1-4). Integrin α2β1 inhibition (TC-I 15) or α2 subunit silencing resulted in augmentation of collagen content within the culture. Expression of and genes was increased in TC-I 15-treated fibroblasts. Total and phosphorylated levels of both FAK and Src kinases were elevated in fibroblasts cultured on stiff substrate. Inhibition of FAK (FAK kinase inhibitor 14) or Src kinase (AZM 47527) increased collagen content within the culture. The substrate stiffness exerted a regulatory influence on collagen metabolism via integrin α2β1 and its downstream signaling (FAK and Src kinases) in cardiac fibroblasts.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10123506