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Relaxin inhibitsrenal myofibroblastdifferentiationviaRXFP1, the nitric oxidepathway, and Smad2 Ishanee MookerjeeTim D. HewitsonMichelle L. Halls2008 год

Relaxin inhibits renal myofibroblast differentiationviaRXFP1, the nitric oxide pathway, and Smad2
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Аннотация: The hormone relaxin inhibits renal myofibroblast differentiation by interfering with TGF-beta1/Smad2 signaling. However, the pathways involved in the relaxin-TGF-beta1/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 approximately 60-70% myofibroblasts were used to determine which relaxin receptors, G-proteins, and signaling pathways were involved in the H2 relaxin-mediated regulation of alpha-smooth muscle actin (alpha-SMA; a marker of myofibroblast differentiation). H2 relaxin only inhibited alpha-SMA immunostaining and collagen concentration in the presence of relaxin family peptide receptor 1 (RXFP1). H2 relaxin also induced a transient rise in cAMP in the presence of G(i/o) inhibition, and a sustained increase in extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. Furthermore, inhibition of neuronal nitric oxide synthase (nNOS), NO, and cGMP significantly blocked the inhibitory effects of relaxin on alpha-SMA and Smad2 phosphorylation, while the NO inhibitor, L-nitroarginine methyl ester (hydrochloride) (L-NAME) significantly blocked the inhibitory actions of relaxin on collagen concentration in vivo. These findings suggest that relaxin signals through RXFP1, and a nNOS-NO-cGMP-dependent pathway to inhibit Smad2 phosphorylation and interfere with TGF-beta1-mediated renal myofibroblast differentiation and collagen production.
Год издания: 2008
Авторы: Ishanee Mookerjee, Tim D. Hewitson, Michelle L. Halls, Roger J. Summers, Michael L. Mathai, Ross A. D. Bathgate, Geoffrey W. Tregear, Chrishan S. Samuel
Издательство: Wiley
Источник: The FASEB Journal
Ключевые слова: Pregnancy-related medical research, Pelvic and Acetabular Injuries
Другие ссылки: The FASEB Journal (HTML)
PubMed (HTML)