Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7080-7085. doi: 10.3892/mmr.2017.7408. Epub 2017 Aug 31.
High glucose (HG) may damage the structure and function of the peritoneal membrane, and is considered to be one of the most important factors that leads to peritoneal fibrosis and ultrafiltration failure. Recently, 1,25(OH)2D3, the active form of vitamin D, was demonstrated to protect against epithelial‑mesenchymal transition and fibrosis in peritoneal mesothelium and other organs. Accumulating evidence has suggested that autophagy serves a protective role in certain diseases by regulating cell survival. The present study examined whether 1,25(OH)2D3 has an effect on autophagy in peritoneal mesothelial cells. The protein level of Beclin, anti‑ubiquitin‑binding protein p62 (p62), microtubule‑associated proteins 1A/1B light chain 3B (LC3-II), mechanistic target of rapamycin (mTOR) and phosphorylated mTOR were evaluated by western blot analysis. Autophagosomes were detected under transmission electron microscopy. It was revealed that exposure to HG inhibited autophagy in peritoneal mesothelial cells. However, 1,25(OH)2D3 alleviated autophagy inhibition induced by HG in human peritoneal mesothelial cells, which activated expression of autophagy‑associated genes encoding Beclin‑1 and LC3-II downregulated the expression of p62 via mTOR signaling pathway. In a mouse model of HG‑treated peritoneal mesothelium, autophagy inhibition was observed in peritoneum, 1,25(OH)2D3 attenuated HG‑induced autophagy inhibition in peritoneal mesothelium via the mTOR signaling pathway. These findings suggested that 1,25(OH)2D3 may be a potential therapy for peritoneal injury.
高葡萄糖（HG）可能会损害腹膜的结构和功能，被认为是导致腹膜纤维化和超滤衰竭的最重要因素之一。最近，维生素 D 的活性形式 1,25(OH)2D3 被证明可防止腹膜间皮和其他器官的上皮-间充质转化和纤维化。越来越多的证据表明，自噬通过调节细胞存活在某些疾病中发挥保护作用。本研究探讨了 1,25(OH)2D3 是否对腹膜间皮细胞的自噬有影响。通过 Western blot 分析评估了 Beclin、抗泛素结合蛋白 p62（p62）、微管相关蛋白 1A/1B 轻链 3B（LC3-II）、雷帕霉素靶蛋白（mTOR）和磷酸化 mTOR 的蛋白水平。在透射电子显微镜下检测自噬体。结果表明，HG 抑制了腹膜间皮细胞的自噬。然而，1,25(OH)2D3 减轻了 HG 诱导的人腹膜间皮细胞自噬抑制，通过 mTOR 信号通路激活自噬相关基因编码的 Beclin-1 和 LC3-II 的表达，下调 p62 的表达。在 HG 处理的腹膜间皮的小鼠模型中，观察到腹膜中的自噬抑制，1,25(OH)2D3 通过 mTOR 信号通路减轻了 HG 诱导的腹膜间皮自噬抑制。这些发现表明 1,25(OH)2D3 可能是腹膜损伤的一种潜在治疗方法。
