u-0126 has been researched along with hispidin* in 1 studies
1 other study(ies) available for u-0126 and hispidin
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Protein kinase C beta overexpression induces fibrotic effects in human proximal tubular epithelial cells.
Cyclosporine A (CsA) significantly improves the success of organ transplantation, however renal fibrosis, characterised by severe tubulointerstitial fibrosis is a complication of CsA therapy. Previously we have reported the involvement of PKC-beta isoforms in a model of CsA-induced tubulointerstitial fibrosis and we have now further elucidated this role. Treatment of human proximal tubular epithelial cells with CsA resulted in increased fibronectin production which coincided with increased PKC activity. To delineate the respective contributions of the two PKC-beta isoforms in fibrotic events, we overexpressed PKC-betaI, -betaII, or both in combination. Overexpression of the two PKC-beta isoforms induced morphological alterations, secretion of the profibrotic cytokine TGF-beta1, and fibronectin release from proximal tubular cells however PKC-betaII induced more significant effects in all parameters examined. Inhibition of PKC-beta completely abrogated the CsA-induced increase in fibronectin secretion demonstrating a direct antifibrotic effect of PKC-beta inhibition. Further studies also identified a role for the p44/42 mitogen activated kinase signalling pathway in CsA-induced fibrotic effects downstream of PKC-beta. Overall, these findings demonstrate a central role for PKC-beta, and particularly PKC-betaII in the development of tubulointerstitial fibrosis and suggest that PKC-beta may be a viable therapeutic target in CsA nephropathy. Topics: Butadienes; Cell Line; Cell Shape; Cyclosporine; Enzyme Activation; Epithelial Cells; Fibronectins; Fibrosis; Green Fluorescent Proteins; Humans; Imidazoles; Isoenzymes; Kidney Tubules, Proximal; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitriles; Phenotype; Protein Kinase C; Protein Kinase C beta; Pyridines; Pyrones; Recombinant Fusion Proteins; Signal Transduction; Transforming Growth Factor beta1 | 2008 |