ERK3 is involved in regulating cardiac fibroblast function

• Published in: Physiological reports Vol. 12; no. 11; pp. e16108 - n/a
• Main Authors: Sahadevan, Pramod, Dingar, Dharmendra, Nawaito, Sherin A., Nair, Reshma S., Trépanier, Joëlle, Sahmi, Fatiha, Shi, Yanfen, Gillis, Marc‐Antoine, Sirois, Martin G., Meloche, Sylvain, Tardif, Jean‐Claude, Allen, Bruce G.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.06.2024; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Aorta; Cardiac function; cardiac remodeling; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cells, Cultured; Collagen; Collagen (type I); Collagen Type I - genetics; Collagen Type I - metabolism; Collagen Type I, alpha 1 Chain - metabolism; ERK3; Fibroblasts; Fibroblasts - metabolism; Growth factors; Haploinsufficiency; Heart; Heart attacks; Hydrogels; Hypertrophy; Immunoreactivity; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Kinases; Laboratories; Lysates; Male; MAP kinase; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - metabolism; Mitogen-Activated Protein Kinase 6 - genetics; Mitogen-Activated Protein Kinase 6 - metabolism; Monoclonal antibodies; Motility; mRNA; Myocardium - cytology; Myocardium - metabolism; Myocytes; Myocytes, Cardiac - metabolism; Original; Penicillin; Peptides; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Proteins; Reagents; Signal transduction; siRNA; TAC; Transforming growth factor-b; Ventricle; motility; fibroblasts; ERK3; hypertrophy; TAC; cardiac remodeling
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.16108

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.