Bone Morphogenetic Protein-2 Antagonizes Renal Interstitial Fibrosis by Promoting Catabolism of Type I Transforming Growth Factor-β Receptors

• DOI: 10.1210/en.2008-0090
• Publication Date: 2008-10-02T01:35:54Z
• Authors: Yu-Lin Yang; Yi-Shiuan Liu; Lea-Yea Chuang; Jinn-Yuh Guh; Tao-Chen Lee; Tung-Nan Liao; Min-Yuan Hung; Tai-An Chiang
• Keywords: Catabolism

TGF-beta is a therapeutic target for renal fibrosis. Scientists have long sought ways to antagonize ameliorate diabetic nephropathy. Bone morphogenetic protein (BMP-2) member of the superfamily and highly regulated in kidney. Thus, role BMP-2 was investigated NRK-49F cells (rat fibroblasts). We showed that TGF-beta1 induces an increase fibronectin. Treatment with exogenous or pCMV-BMP-2 significantly reversed TGF-beta1-induced fibronectin concomitant significant decrease type I receptors (TGF-beta RI). Moreover, shortened half-life RI. These results are related proteosomal activation because MG132, proteasome inhibitor, abolished BMP-2-mediated degradation This confirmed time course dependently enhanced ubiquitination level In addition, Smads would seem be involved interaction TGF-beta. demonstrated pSmad2/3 inhibitory Smad7. Most importantly, Smad7 small interfering RNA BMP-2-induced evaluated clinical efficacy using unilateral ureteral obstruction rats. administered ip 7 d. kidneys, interstitial fibrosis prominent. However, treatment dramatically reduced Masson's trichrome staining (collagen) tubular areas kidneys concomitantly reduction suggest acts as novel antagonizing cytokine partly by down-regulating RI Smads.