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J Zhejiang Univ (Med Sci)  2021, Vol. 50 Issue (5): 627-632    DOI: 10.3724/zdxbyxb-2021-0242
Metformin alleviates intestinal epithelial barrier damage by inhibiting endoplasmic reticulum stress-induced cell apoptosis in colitis cell model
WANG Jingang1,2,CHEN Chunxiao1,*(),REN Yuhan2,ZHOU Xinxin1,YU Shan2
1. Department of Gastroenterology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
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
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Objective:To investigate the effect and mechanism of metformin on intestinal epithelial barrier injury in ulcerative colitis. Methods: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 1?mmol/L for 24?h. 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. Results: After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22±2.34)% to (9.88±0.61)% (t=3.119, P<0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (t=5.172 and 3.546, both P<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 (allP<0.05).Conclusion: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.

Key wordsColitis, ulcerative      Metformin      Endoplasmic reticulum stress      Apoptosis      Co-culture cell      Tight junction protein     
Received: 10 July 2021      Published: 29 December 2021
CLC:  R310.17  
Corresponding Authors: CHEN Chunxiao     E-mail:
Cite this article:

WANG Jingang,CHEN Chunxiao,REN Yuhan,ZHOU Xinxin,YU Shan. Metformin alleviates intestinal epithelial barrier damage by inhibiting endoplasmic reticulum stress-induced cell apoptosis in colitis cell model. J Zhejiang Univ (Med Sci), 2021, 50(5): 627-632.

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关键词: 结肠炎, 溃疡性,  二甲双胍,  内质网应激,  细胞凋亡,  细胞共培养,  紧密连接蛋白 
Figure 1 The flow cytometry analysis of intestinal epithelial cell apoptosis in model group and metformin group
Figure 2 Electrophoregrams of tight junction proteins in model group and metformin group
Figure 3 Electrophoregrams of endoplasmic retculum stress associated proteins in model group and metformin group


































Table 1 Expression of endoplasmic reticulum stress associated proteins in model group and metformin group
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