Relaxin modulates fibroblast function, collagen production, and matrix metalloproteinase-2 expression by cardiac fibroblasts.
Cardiac fibrosis is a hallmark of heart disease and involves recruitment, proliferation, and differentiation of extracellular matrix-producing fibroblasts, leading to overproduction of collagen within the myocardium. In this study, the effects of relaxin in inhibiting these processes were investigated. We used neonatal rat atrial and ventricular fibroblasts, which respond to pro-fibrotic stimuli (i.e., transforming growth factor-beta and angiotensin II) and naturally express the relaxin receptor LGR7. Relaxin significantly inhibited TGF-beta- and angiotensin II-mediated fibroblast function and collagen production over a 72-h period, while increasing MMP-2 expression and activity in the presence of both profibrotic factors (all P < .05). These studies demonstrate that relaxin may have therapeutic potential in diseased states characterized by cardiac fibrosis.
Mookerjee
Ishanee
I
Howard Florey Institute of Experimental Physiology & Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
Unemori
Elaine N
EN
DU
Xiao-Jun
XJ
Tregear
Geoffrey W
GW
Samuel
Chrishan S
CS
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D012065:Relaxin; D003094:Collagen; D020778:Matrix Metalloproteinase 2