Investigations into the inhibitory effects of relaxin on renal myofibroblast differentiation.
Derived from fibroblasts, myofibroblasts are the principal cells that are responsible for the synthesis and reorganization of excess matrix in renal interstitial fibrosis. Recognized from their de novo expression of alpha-smooth muscle actin, myofibroblast differentiation and activity can be influenced by several factors, including a combination of growth factors and other soluble mediators, extracellular matrix components, and mechanical stress. Relaxin has previously been shown to inhibit renal myofibroblast differentiation in vitro, an effect partly mediated through its ability to interfere with the transforming growth factor-beta1 (TGF-beta1) pathway via inhibition of Smad2 phosphorylation and translocation. Furthermore, endogenous relaxin has been shown to protect the kidney from a myofibroblast-mediated model of injury in vivo. However, the pathways involved in the interaction between relaxin and TGF-beta1 remain unknown. In this report, the inhibitory actions of relaxin on TGF-beta1-induced renal myofibroblast differentiation are summarized to date, and the potential signaling pathways that are implicated in relaxin's inhibitory actions are discussed.
Samuel
Chrishan S
CS
Department of Biochemistry and Molecular Biology, Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia. chrishan.samuel@florey.edu.au
Mookerjee
Ishanee
I
Halls
Michelle L
ML
Summers
Roger J
RJ
Chew
Elaine
E
Bathgate
Ross A D
RA
Tregear
Geoffrey W
GW
Hewitson
Tim D
TD
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology*; D007668:Kidney / Q000166:cytology*; D012065:Relaxin / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D000199:Actins; D053773:Transforming Growth Factor beta1; D012065:Relaxin