title: Production and degradation of extracellular matrix in reversible glomerular lesions in rat model of habu snake venom-induced glomerulonephritis.
abstract: We investigated the mechanism of development and repair process of glomerular injury in a rat model of habu snake (Trimeresurus flavoviridis) venom (HSV)-induced glomerulonephritis. Glomerulonephritis was induced in rats by intravenously injecting HSV at 3 mg/kg. Renal tissue was isolated and subjected to immunohistochemical analysis for expression levels of type IV collagen, heat shock protein 47 (HSP47), transforming growth factor-β (TGF-β), and matrix metalloproteinase-3 (MMP-3), as well as its transcription factor Ets-1. Expression levels of HSP47, TGF-β, and type IV collagen began to increase in the mesangial area starting from day 14 and peaked on day 21, followed by a gradual decrease. Expression levels of MMP-3 and Ets-1 started to increase coinciding with peak production of mesangial matrix on day 21, peaking on day 35, followed by gradual decrease. Expression of MMP-3 and Ets-1 persisted until day 63, whereas that of HSP47 and type IV collagen returned to baseline level at this time point. Time-course changes of extracellular matrix (ECM) accumulation in glomeruli in the HSV-induced glomerulonephritis model were correlated with those of factors involved in both ECM production and degradation systems. Continued expression of factors in the degradation system seems particularly important for the repair process. These findings might lead to new therapies that prevent and repair glomerular injury.
authors.affiliation: Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Tayo
authors.initials: T
authors.lastname: Kawazu
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nishino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obata
authors.forename: Akira
authors.initials: A
authors.lastname: Furusu
authors.forename: Masanobu
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Katsushige
authors.initials: K
authors.lastname: Abe
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D024141:Collagen Type IV / Q000378:metabolism; D003435:Crotalid Venoms / Q000633:toxicity*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D017841:Trimeresurus
chemical_list: D024141:Collagen Type IV; D003435:Crotalid Venoms; C494043:Ets1 protein, rat; D050958:HSP47 Heat-Shock Proteins; D050784:Proto-Oncogene Protein c-ets-1; C494662:Serpinh1 protein, rat; D016212:Transforming Growth Factor beta; D019278:Matrix Metalloproteinase 3