title: Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells.
abstract: Fibrin formation within the glomeruli occurs in various forms of human and experimental glomerulonephritis and it may play an important role in progressive glomerular injury. Transforming growth factor-beta (TGF-beta) has been shown to participate in the glomerular accumulation of extracellular matrix in glomerulonephritis. We investigated whether thrombin, an important coagulation factor, could modulate the production of TGF-beta by cultured human mesangial cells (HMC). TGF-beta levels in the culture supernatants were measured by ELISA using a specific antibody. The TGF-beta concentration was significantly increased by incubation of HMC with thrombin in a time-dependent manner. The stimulating effect of thrombin on TGF-beta was inhibited by addition of hirudin (a natural thrombin inhibitor) and argatroban (a synthetic thrombin inhibitor). In addition DFP-inactivated thrombin, which has no enzymatic activity, did not stimulate TGF-beta production. A protein kinase C inhibitor (H7) and a tyrosine kinase inhibitor (herbimycin A) also inhibited thrombin induced TGF-beta production. These findings suggested that thrombin may modulate the synthesis of TGF-beta via protein kinase C- and tyrosine kinase-dependent mechanisms in cultured HMC. Thus thrombin may participate in the accumulation of extracellular matrix in glomeruli through the augmentation of TGF-beta production.
authors.affiliation: Second Department of Internal Medicine, Hirosaki University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamabe
authors.forename: H
authors.initials: H
authors.lastname: Osawa
authors.forename: H
authors.initials: H
authors.lastname: Inuma
authors.forename: M
authors.initials: M
authors.lastname: Kaizuka
authors.forename: N
authors.initials: N
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Y
authors.initials: Y
authors.lastname: Baba
authors.forename: K
authors.initials: K
authors.lastname: Shirato
authors.forename: K
authors.initials: K
authors.lastname: Onodera
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D013917:Thrombin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D016212:Transforming Growth Factor beta; D013917:Thrombin