Cell-specific ablation of Hsp47 defines the collagen-producing cells in the injured heart

JCI Insight
Hadi KhalilJeffery D Molkentin

Abstract

Collagen production in the adult heart is thought to be regulated by the fibroblast, although cardiomyocytes and endothelial cells also express multiple collagen mRNAs. Molecular chaperones are required for procollagen biosynthesis, including heat shock protein 47 (Hsp47). To determine the cell types critically involved in cardiac injury–induced fibrosis theHsp47 gene was deleted in cardiomyocytes, endothelial cells, or myofibroblasts. Deletion ofHsp47 from cardiomyocytes during embryonic development or adult stages, or deletion from adult endothelial cells, did not affect cardiac fibrosis after pressure overload injury. However, myofibroblast-specific ablation of Hsp47; blocked fibrosis and deposition of collagens type I, III, and V following pressure overload as well as significantly reduced cardiac hypertrophy. Fibroblast-specific Hsp47-deleted mice showed lethality after myocardial infarction injury, with ineffective scar formation and ventricular wall rupture. Similarly, only myofibroblast-specific deletion of Hsp47reduced fibrosis and disease in skeletal muscle in a mouse model of muscular dystrophy. Mechanistically, deletion of Hsp47 from myofibroblasts reduced mRNA expression of fibrillar collagens and attenuated their ...Continue Reading

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Citations

Aug 15, 2019·Circulation Research·Matthew S StrattonTimothy A McKinsey
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Datasets Mentioned

BETA
GSE129612

Methods Mentioned

BETA
transgenic
FACS
genotyping
electrophoresis
flow cytometry
Profiler
PCR

Software Mentioned

FACSDiva
NIS
AltAnalyze
Leica Application Suite
elements
NIS Elements AR
Adobe Photoshop Elements

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