ERK3 is involved in regulating cardiac fibroblast function.

Autor: Sahadevan P; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada., Dingar D; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada., Nawaito SA; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Pharmacology and Physiology, Université de Montréal, Montréal, Québec, Canada.; Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt., Nair RS; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada., Trépanier J; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada., Sahmi F; Montreal Heart Institute, Montréal, Québec, Canada., Shi Y; Montreal Heart Institute, Montréal, Québec, Canada., Gillis MA; Montreal Heart Institute, Montréal, Québec, Canada., Sirois MG; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Pharmacology and Physiology, Université de Montréal, Montréal, Québec, Canada., Meloche S; Department of Pharmacology and Physiology, Université de Montréal, Montréal, Québec, Canada.; Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, Canada., Tardif JC; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Medicine, Université de Montréal, Montréal, Québec, Canada., Allen BG; Montreal Heart Institute, Montréal, Québec, Canada.; Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec, Canada.; Department of Pharmacology and Physiology, Université de Montréal, Montréal, Québec, Canada.; Department of Medicine, Université de Montréal, Montréal, Québec, Canada.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2024 Jun; Vol. 12 (11), pp. e16108.
DOI: 10.14814/phy2.16108
Abstrakt: ERK3/MAPK6 activates MAP kinase-activated protein kinase (MK)-5 in selected cell types. Male MK5 haplodeficient mice show reduced hypertrophy and attenuated increase in Col1a1 mRNA in response to increased cardiac afterload. In addition, 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 diameter 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 motility in both atrial and ventricular myofibroblasts. These results suggest that ERK3 plays an important role in multiple aspects of cardiac fibroblast biology.
(© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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