Cardiomyocyte-derived HSPB1 regulates TGF-β1 maturation and inhibits endothelial-to-mesenchymal transition in myocardial fibrosis
Jia Wang, Aoni Fu, Guoliang Tan, Haotian Yang, Jiang Zhou, Jianqiang Peng, Qinghai Zhang, Xiehong Liu
TL;DR
This study shows that a protein called HSPB1 in heart muscle cells helps reduce heart scarring after a heart attack by controlling TGF-β1 activity and preventing harmful cell changes.
Contribution
The study reveals a novel mechanism where cardiomyocyte HSPB1 regulates TGF-β1 maturation and inhibits EndoMT in myocardial fibrosis.
Findings
HSPB1 overexpression in cardiomyocytes reduces collagen buildup and improves heart function after infarction.
HSPB1 limits disulfide bond formation in pro-TGF-β1, reducing mature TGF-β1 secretion.
HSPB1 inhibits TGF-β1/Smad2/3 signaling, which suppresses endothelial-to-mesenchymal transition.
Abstract
Myocardial fibrosis after myocardial infarction is promoted by endothelial-to-mesenchymal transition (EndoMT) driven by TGF-β1. We investigated whether cardiomyocyte heat shock protein B1 (HSPB1) shapes this pathway. In mouse infarction models, cardiomyocyte-targeted HSPB1 overexpression reduced collagen deposition and preserved ventricular function, whereas HSPB1 knockdown exacerbated fibrosis and EndoMT activation. In endothelial assays, HSPB1 attenuated TGF-β1–induced Smad2/3 phosphorylation and mesenchymal marker expression. Mechanistically, HSPB1 modulated redox conditions to restrain disulfide-bond formation during pro-TGF-β1 maturation, reducing the secretion of mature TGF-β1. These results link cardiomyocyte redox homeostasis with paracrine control of endothelial plasticity and support HSPB1 as a therapeutic entry point to limit post-infarction fibrotic remodeling.…
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Taxonomy
TopicsCardiac Fibrosis and Remodeling · Heat shock proteins research · Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis