Mechanisms of Gancao Xiexin Decoction on protecting intestinal epithelial cell barrier under stress state by regulating PERK-elF2α-CHOP signaling pathway
10.3969/j.issn.1001-1978.2021.05.022
- Author:
Yan SHEN
1
;
Ji-Hong ZHONG
1
;
Si-Yi NI
1
;
Bin LYU
2
Author Information
1. Dept of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University
2. Dept of Gastroenterology, Zhejiang Provincial Hospital of Chinese Medical
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum stress;
Gancao Xiexin Decoction;
intestinal epithelial cells;
intestinal mucosal barrier;
PERK-elF2α-CHOP signaling pathway;
tunicamycin;
ulcerative colitis
- From:
Chinese Pharmacological Bulletin
2021;37(5):717-723
- CountryChina
- Language:Chinese
-
Abstract:
Aim To observe the protective effect of Gancao Xiexin Decoction (GXD) on intestinal epithelial cells (IECs) under endoplasmic reticulum stress from the perspective of PERK-elF2α-CH0P signaling pathway. Methods Caco-2 cells were cultured and divided into normal control group (NC), model control group(MC), low-dose GXD group(GXD-L), mediumdose GXD group (GXD-M) and high-dose GXD group (GXD-H). Models of the stress epithelial cells were induced by tunicamycin(Tm), and GXD groups were treated with GXD contained serum at the same time. The cell survival rate was assessed by CCK-8 method, the cell apoptotic rate and cell cycle distribution were determined by flow cytometry, and the cell barrier permeability was determined by TEER and FITC-dextran method; the expression levels of core proteins of PERK-elF2α-CH0P signaling pathway were detected by Western blot. Results Compared with MC group, GXD intervention could improve cell survival rate(P < 0. 05), reduce their apoptotic rate(P <0. 01), relieve cell cycle arrest(P < 0. 01), improve cell barrier permeability by increasing cell TEER value (P < 0. 01) and decreasing FITC-dextran concentration (P < 0.05), and the levels of p-PERK, p-elF2α, ATF4 and CHOP in GXD-M and GXD-H groups all visibly descended (P < 0. 01). Conclusions GXD can reduce the excessive apoptosis of IECs and protect intestinal epithelial cell barrier homeostasis by inhibiting the signal transduction of PERK-elF2α-CH0P apoptotic pathway.
