Journal Article

Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells.

H Yamabe, H Osawa, H Inuma, M Kaizuka, N Tamura, S Tsunoda, Y Baba, K Shirato and K Onodera

in Nephrology Dialysis Transplantation

Volume 12, issue 3, pages 438-442
Published in print March 1997 | ISSN: 0931-0509
Published online March 1997 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/12.3.438
Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells.

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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.

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Subjects: Nephrology

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