Department of Nephrology, First Hospital of China Medical University, 155 North Nanjing Street, Shenyang City, Liaoning Province 110001, People's Republic of China.
Pharmacol Rep. 2011;63(5):1137-44. doi: 10.1016/s1734-1140(11)70632-6.
Mesangial cells are the main source of renal interstitial fibrosis in diabetic nephropathy (DN). Interferon-γ (IFN-γ) is a key cytokine that may play a potential therapeutic role in reducing fibrosis. Here, we focus on the effects of IFN-γ on human mesangial cells (HMCs) treated with high glucose. This study shows that IFN-γ phosphorylates STAT1, suppresses HMC proliferation, and downregulates mRNA and protein levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in HMCs treated with high glucose. The regulation of P-STAT1 could change HMC proliferation and the expression of fibrotic cytokines TGF-β1 and CTGF in HMCs. These data indicate that IFN-γ could activate STAT1 to suppress the increase in TGF-β1 and CTGF synthesis in HMCs induced by high glucose. This paper may lead to new therapeutic treatments of DN.
肾小球系膜细胞是糖尿病肾病（DN）中肾间质纤维化的主要来源。干扰素-γ（IFN-γ）是一种关键的细胞因子，可能在减少纤维化方面发挥潜在的治疗作用。在这里，我们专注于 IFN-γ对高糖处理的人肾小球系膜细胞（HMC）的影响。本研究表明，IFN-γ使 STAT1 磷酸化，抑制 HMC 增殖，并下调高糖处理的 HMC 中转化生长因子-β1（TGF-β1）和结缔组织生长因子（CTGF）的 mRNA 和蛋白水平。P-STAT1 的调节可以改变 HMC 的增殖以及 TGF-β1 和 CTGF 等纤维化细胞因子在 HMC 中的表达。这些数据表明，IFN-γ可以激活 STAT1 抑制高糖诱导的 HMC 中 TGF-β1 和 CTGF 合成的增加。本文可能为 DN 的新治疗方法开辟道路。
