Effect of 1,25(OH)2D3 on high glucose‑induced autophagy inhibition in peritoneum.

Abstract

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.

• Authors: Lina Yang, Yi Fan, Xiuli Zhang, Jin Liu, Jianfei Ma
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 16 Issue 5 Pg. 7080-7085 (Nov 2017) ISSN: 1791-3004 [Electronic] Greece
• PMID: 28901396 (Publication Type: Journal Article)

Chemical References

• Beclin-1
• Microtubule-Associated Proteins
• Sequestosome-1 Protein
• TOR Serine-Threonine Kinases
• Calcitriol
• Glucose

Topics

• Animals
• Autophagy (drug effects)
• Beclin-1 (metabolism)
• Calcitriol (pharmacology)
• Cell Line
• Epithelial Cells (cytology, drug effects, metabolism)
• Glucose (toxicity)
• Humans
• Male
• Mice
• Microscopy, Electron, Transmission
• Microtubule-Associated Proteins (metabolism)
• Peritoneal Dialysis
• Peritoneum (cytology)
• Sequestosome-1 Protein (metabolism)
• TOR Serine-Threonine Kinases (metabolism)