Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6142-6147. doi: 10.3892/mmr.2017.7388. Epub 2017 Aug 29.
Podocytes serve a critical role in the development of many glomerular diseases, including diabetic nephropathy (DN). Epigallocatechin‑3‑gallate (EGCG), a predominant polyphenolic component of green tea, has indicated its therapeutic effects in diabetes. In the present study, mouse podocyte cells were cultured in vitro, cell injury was induced by high glucose, and the protective effect of EGCG on cell proliferation and apoptosis and the underlying mechanisms were investigated. The results demonstrated that high glucose significantly inhibited cell proliferation after 48 and 72 h compared with normal glucose and mannitol treatment. EGCG (20 µmol/l) markedly promoted podocyte proliferation after 24, 48 and 72 h incubation with high glucose. Furthermore, high glucose significantly reduced WT‑1 and nephrin expression in podocytes compared with the normal glucose and mannitol groups, while EGCG (20 µmol/l) treatment largely restored their expression. High glucose also significantly increased the apoptotic cell population compared with normal glucose and mannitol groups. However, EGCG combined with high glucose greatly decreased the apoptotic cell number compared with high glucose treatment alone. Furthermore, high glucose treatment was demonstrated to significantly increase glucose‑regulated protein 78 (GRP78), phosphorylated‑ PKR‑like ER kinase (p‑PERK) and caspase‑12 protein expression levels, which is representative of endoplasmic reticulum (ER) stress, compared with the normal glucose and mannitol groups. However, EGCG treatment significantly attenuated GRP78, p‑PERK and caspase‑12 protein expression induced by high glucose. These findings suggested that EGCG serves a protective role in glucose‑induced podocyte apoptosis via suppressing ER stress, and may provide a novel therapeutic strategy to ameliorate the process of DN.
足细胞在许多肾小球疾病的发生发展中起着关键作用，包括糖尿病肾病（DN）。表没食子儿茶素没食子酸酯（EGCG）是绿茶中主要的多酚类成分，已显示出其在糖尿病中的治疗作用。在本研究中，体外培养小鼠足细胞，用高糖诱导细胞损伤，探讨 EGCG 对细胞增殖和凋亡的保护作用及其机制。结果表明，与正常葡萄糖和甘露醇处理相比，高葡萄糖显著抑制 48 和 72 小时后的细胞增殖。EGCG（20µmol/L）孵育 24、48 和 72 小时后，明显促进高糖诱导的足细胞增殖。此外，与正常葡萄糖和甘露醇组相比，高葡萄糖显著降低了足细胞中 WT-1 和nephrin 的表达，而 EGCG（20µmol/L）处理则在很大程度上恢复了它们的表达。与正常葡萄糖和甘露醇组相比，高葡萄糖也显著增加了凋亡细胞的数量。然而，与高葡萄糖单独处理相比，EGCG 与高葡萄糖联合处理大大降低了凋亡细胞的数量。此外，高葡萄糖处理显著增加葡萄糖调节蛋白 78（GRP78）、磷酸化蛋白激酶 R 样内质网激酶（p-PERK）和半胱氨酸天冬氨酸蛋白酶-12（caspase-12）蛋白的表达水平，这代表内质网（ER）应激，与正常葡萄糖和甘露醇组相比。然而，EGCG 处理显著减弱了高葡萄糖诱导的 GRP78、p-PERK 和 caspase-12 蛋白的表达。这些发现表明，EGCG 通过抑制内质网应激在葡萄糖诱导的足细胞凋亡中发挥保护作用，可能为改善 DN 过程提供一种新的治疗策略。
