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Interferon-γ Reverses High Glucose or AGE-induced Effects in NRK-49F Cells

丙型干擾素逆轉高糖及高度糖化終產物對NRK-49F細胞的效果

並列摘要


Diabetic nephropathy (DN) is characterized by renal hyperplasia/hypertrophy culminating in renal fibrosis (glomerulosclerosis and tubulointerstiial fibrosis). Interstitial fibroblast proliferation is a prominent feature of interstitial fibrosis. Thus, we had shown that advanced glycation end-product (AGE) induced cellular proliferation in NRK-49F (normal rat interstitial fibroblast) cell line. Interferon-γ (IFN-γ) had been shown by others to inhibit fibroblast proliferation. Therefore, we studied whether IFN-γ reversed high glucose (200-500mg/dl) or AGE(100-422μg/ml) –induced effects in NRK-49F cells. Results: In NRK-49F cells, glucose and AGE dose-dependently and time-dependently (1-7 days) increased cellular proliferation. Angiotensin II (AII) also dose-dependently (10-5 -1o 10-9 M) increased cellular proliferation Conversely, transforming growth factor-ß1 (TGF-ß1 0.1 -10 ng/ml) and IFN-γ(100-10,000 U/ml) dose-dependently decreased cellular proliferation at 3 days. Interestingly, IFN-γ(1,000 U/ml) reversed high glucose (500 mg/dl),AGE(200 μg/ml) and AII (10-7 M)-induced cellular proliferation. IFN-γ(1,000 U/ml) also reversed TGF-ß1 (1 ng/ml)-induced inhibition of proliferation. In contrast, INF-γ was ineffective at reversing high glucose, AGE or AII-induced growth effects in a LLC-PL1(porcine proximal tubule-like) cell line. Conclusion: IFN-γ was effective in reversing high glucose, AGE and AII-induced growth effects in NRK-49F cells. Because IFN-γ had been shown to be effective in pulmonary and hepatic fibrosis in animal models, we speculate that IFN-γ may also be effective in models of renal fibrosis, including the late stages of DN.

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