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• W2897636161 abstract "Objectives The aim of this study was to evaluate the role of angiotensin II (AT-II) and its main mediator, transforming growth factor beta 1 (TGF-β1), in the development of feline renal fibrosis. Methods Expression of marker genes indicating epithelial-to-mesenchymal transition (EMT), profibrotic mediators and matricellular proteins was measured in feline kidney epithelial cells (Crandell Rees feline kidney [CRFK] cells) after incubation with AT-II and/or TGF-β1. Results Cells incubated with TGF-β1 or the combination of TGF-β1 with AT-II showed clear EMT with more stretched fibroblastic cells, whereas the cells incubated without TGF-β1 and AT-II (control) showed more epithelial cells. Gene expression of collagen type I ( COL1), tenascin-C ( TNC), trombospondin-1 ( TSP-1), connective tissue growth factor ( CTGF) and alpha-smooth muscle actin ( α-SMA) increased significantly after incubation of the CRFK cells with TGF-β1 or TGF-β1 in combination with AT-II for 12 h. As incubation of the CRFK cells with only AT-II did not show any significant rise in gene expression of the above-mentioned genes, this was further investigated. In contrast to healthy feline kidney tissue, CRFK cells showed almost no expression of the AT-II type 1 (AT 1 ) receptor. Conclusions and relevance TGF-β1 significantly induced expression of the EMT marker gene α-SMA, profibrotic mediator CTGF, and fibrogenic proteins COL1, TNC and TSP-1 in CRFK cells. The effect of TGF-β1 on myofibroblast formation was also observed by the stretched appearance of the CRFK cells. As CRFK cells expressed almost no AT 1 receptors, this cell line proved not suitable for testing the efficacy of drugs that interact with the AT 1 receptor. As AT-II stimulates the effects of TGF-β1 in mammals, the results of this study suggest an indirect profibrotic effect of AT-II besides the demonstrated profibrotic effect of TGF-β1 and thus the development of feline renal fibrosis. Modulation of EMT or proliferation of myofibroblasts could serve as a diagnostic tool and a novel therapeutic target to inhibit renal fibrogenesis, and could possibly serve in the therapy of feline renal fibrosis." @default.
• W2897636161 created "2018-10-26" @default.
• W2897636161 creator A5016058721 @default.
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• W2897636161 date "2018-10-22" @default.
• W2897636161 modified "2023-09-26" @default.
• W2897636161 title "Profibrotic effects of angiotensin II and transforming growth factor beta on feline kidney epithelial cells" @default.
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• W2897636161 doi "https://doi.org/10.1177/1098612x18805862" @default.
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