title: Relaxin increases ubiquitin-dependent degradation of fibronectin in vitro and ameliorates renal fibrosis in vivo.
abstract: Fibronectin, a large adhesive glycoprotein, is a prominent constituent of the extracellular matrix. Abnormalities in fibronectin homeostasis occur in numerous disease states, ranging from primary fibrosing conditions to neoplastic transformation. We demonstrate that fibronectin is a target protein substrate for ubiquitin-dependent degradation. Coimmunoprecipitation experiments and confocal microscopy demonstrated ubiquitin-fibronectin interaction. In an in vitro model of renal fibrosis, relaxin, an insulin-like growth factor, increased ubiquitin-dependent fibronectin degradation. Relaxin also was evaluated in an anti-glomerular basement membrane model of renal fibrosis. Animals treated with relaxin experienced renoprotection, manifested by decreased serum creatinine and proteinuria. Histological evaluation of kidney sections from animals treated with relaxin showed decreased glomerulosclerosis and interstitial fibrosis. We conclude that relaxin might be developed as a useful agent for the treatment of renal fibrosis.
authors.affiliation: Division of Renal Diseases and Hypertension, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. Glenn.A.McDonald@uth.tmc.edu
authors.forename: Glenn A
authors.initials: GA
authors.lastname: McDonald
authors.forename: Pradip
authors.initials: P
authors.lastname: Sarkar
authors.forename: Helmut
authors.initials: H
authors.lastname: Rennke
authors.forename: Elaine
authors.initials: E
authors.lastname: Unemori
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
authors.forename: Vikas P
authors.initials: VP
authors.lastname: Sukhatme
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism*; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism*; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012065:Relaxin / Q000494:pharmacology* / Q000627:therapeutic use*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D025801:Ubiquitin; D012313:RNA; D012065:Relaxin