Objective To explore effects of exendin-4 on the metabolism of extracellular matrix (ECM) in human mesangial cells (HMC) cultured in the presence of high glucose and explore the possible mechanism. Methods Human mesangial cells (HMC) were treated with exendin-4 under high glucose conditions. The cell proliferation was observed using CCK8 assay, and the expressions of collagen type I, fibronectin, transforming growth factor-β1 (TGFβ1) expression and extracellular signal-regulated kinase (ERK) signaling pathway activity were assessed using Western blotting. Results Exendin-4 inhibited cell proliferation and the expressions of collagen type I, fibronectin and TGFβ1 and reversed ERK phosphorylation in high glucose-induced HMC. Conclusion Exendin-4 can regulate ECM metabolism in HMC cultured in high glucose by inhibiting TGFβ1/ERK pathway, suggesting the beneficial effects of exendin-4 in preventing and treating diabetic nephropathy.%目的：探讨exendin-4对高糖条件下人系膜细胞（HMC）细胞外基质（ECM）代谢的影响及其可能的机制。方法取对数生长期的HMC分为正常对照（NG）组、渗透压对照（Man）组、高糖（HG）组和高糖联合不同浓度exendin-4（1、10、100 nmol/L）组。体外培养HMC，采用cck8法测24 h HMC增殖情况；Western Blotting检测细胞培养15 min后细胞外调节激酶（ERK）/p-ERK蛋白表达情况，24 h后Ⅰ型胶原、纤维连接蛋白（FN）、转化生长因子β1（TGF-β1）蛋白表达情况。结果 CCK-8结果显示高糖诱导HMC 24 h后可见细胞增殖明显增强（1±0.06 vs 1.20±0.07，P<0.001），加入exendin-4后可抑制细胞增殖（1.12±0.02 vs 1.20±0.07，P<0.05，1.05±0.08 vs 1.20±0.07，P<0.001）。细胞培养24 h后，与NG组相比，HG组细胞Ⅰ型胶原、FN、TGF-β1蛋白表达量均显著增加（P<0.001）；与HG组相比，高糖联合exendin-4组Ⅰ型胶原、FN、TGF-β1蛋白表达量均显著降低（P<0.01）。细胞培养15 min后，与NG组相比，HG组细胞ERK磷酸化蛋白表达量较NG组显著增加（P<0.001）；与HG组相比，高糖联合exendin-4组ERK磷酸化蛋白表达量显著下降（P<0.001）。渗透压对照组与正常对照组各指标间差异均无统计学意义。结论 Exendin-4可能通过抑制TGF-β1/ERK通路活性对高糖条件下HMC ECM代谢起到了保护性的调节作用。
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