Metformin alleviates intestinal epithelial barrier damage by inhibiting endoplasmic reticulum stress-induced cell apoptosis in colitis cell model.
10.3724/zdxbyxb-2021-0242
- Author:
Jingang WANG
1
;
Chunxiao CHEN
1
;
Yuhan REN
1
;
Xinxin ZHOU
1
;
Shan YU
1
Author Information
1. 2. Department of Gastroenterology, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, Shengzhou People's Hospital, Shengzhou 312400, Zhejiang Province, China.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Co-culture cell;
Colitis, ulcerative;
Endoplasmic reticulum stress;
Metformin;
Tight junction protein
- MeSH:
Apoptosis;
Caco-2 Cells;
Colitis, Ulcerative;
Endoplasmic Reticulum Stress;
Humans;
Metformin/pharmacology*
- From:
Journal of Zhejiang University. Medical sciences
2021;50(5):627-632
- CountryChina
- Language:English
-
Abstract:
To investigate the effect and mechanism of metformin on intestinal epithelial barrier injury in ulcerative colitis. A cell model of colitis was established by co-culture of human colon cancer cell line Caco-2 and human monocyte cell line THP-1. The colitis model cells were treated with metformin at concentration of for Flow cytometry was used to detect Caco-2 cell apoptosis, and Western blotting was used to detect the protein expression of tight junction proteins and endoplasmic reticulum stress-related proteins. After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22±2.34)% to 0.61)% (=3.119, <0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (=5.172 and 3.546, both <0.05). In addition, the expression levels of endoplasmic reticulum-related proteins glucose regulated protein (GRP) 78, C/EBP homologous protein (CHOP) and caspase-12, as well as the phosphorylation level of PRKR-like endoplasmic reticulum kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) decreased (all <0.05). Metformin may alleviate the intestinal epithelial barrier damage in colitis by reducing intestinal epithelial cell apoptosis and increasing the expression of tight junction proteins, which may be associated with the inhibition of endoplasmic reticulum stress-induced apoptotic pathway.
