Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and Smad2

Abstract

The hormone relaxin inhibits renal myofibroblast differentiation by interfering with TGF-β1/Smad2 signaling. However, the pathways involved in the relaxin-TGF-β1/Smad2 interaction remain unknown. This study investigated the signaling mechanisms by which human gene-2 (H2) relaxin regulates myofibroblast differentiation in vitro by examining its effects on mixed populations of fibroblasts and myofibroblasts propagated from injured rat kidneys. Cultures containing ∼60-70% myofibroblasts were used to determine which relaxin receptors, G-proteins, and signaling pathways were involved in the H2 relaxin-mediated regulation of α-smooth muscle actin (α-SMA; a marker of myofibroblast differentiation)...