Featured Publication in Focus: ERK3 is involved in regulating cardiac fibroblast function
Jul 22 , 2024
Authors:
Pramod Sahadevan, Dharmendra Dingar, Sherin A. Nawaito, Reshma S. Nair, Joëlle Trépanier,Fatiha Sahmi, Yanfen Shi, Marc-Antoine Gillis, Martin G. Sirois, Sylvain Meloche, Jean-Claude Tardif and Bruce G. Allen
Montreal Heart Institute, Montréal, Québec, Canada
Europe PMC. The Physiological Society. Physiological Reports
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Product referenced:
Catalogue # 203002-1
Collagen Type I Antibody, anti-Mouse, 100 uL
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ABSTRACT
ERK3/MAPK6 activates MAP kinase-activated protein kinase (MK)-5 in selected cell types. Male MK5 haplodeficient mice show reduced hypertrophy and attenu- ated increase in Col1a1 mRNA in response to increased cardiac afterload. In addi- tion, MK5 deficiency impairs cardiac fibroblast function. This study determined the effect of reduced ERK3 on cardiac hypertrophy following transverse aortic constriction (TAC) and fibroblast biology in male mice. Three weeks post-surgery, ERK3, but not ERK4 or p38α, co-immunoprecipitated with MK5 from both sham and TAC heart lysates. The increase in left ventricular mass and myocyte di- ameter was lower in TAC-ERK3+/− than TAC-ERK3+/+ hearts, whereas ERK3 haploinsufficiency did not alter systolic or diastolic function. Furthermore, the TAC-induced increase in Col1a1 mRNA abundance was diminished in ERK3+/− hearts. ERK3 immunoreactivity was detected in atrial and ventricular fibroblasts but not myocytes. In both quiescent fibroblasts and “activated” myofibroblasts isolated from adult mouse heart, siRNA-mediated knockdown of ERK3 reduced the TGF-β-induced increase in Col1a1 mRNA. In addition, intracellular type 1 collagen immunoreactivity was reduced following ERK3 depletion in quiescent fibroblasts but not myofibroblasts. Finally, knocking down ERK3 impaired motil- ity in both atrial and ventricular myofibroblasts. These results suggest that ERK3 plays an important role in multiple aspects of cardiac fibroblast biology.
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