The suppressor of cytokine signaling SOCS1 promotes apoptosis of intestinal epithelial cells via p53 signaling in Crohn's disease.

Abstract

The suppressor of cytokine signaling SOCS1 is a member of the cytokine signaling pathway inhibitor family, which is induced by the IFN-γ induced JAK signaling pathway. The expression of SOCS1 has been found to increase in Crohn's disease (CD) patients, but the role of SOCS1 in intestinal epithelium is unclear. This study was designed to investigate whether SOCS1 has a role in the death of intestinal epithelial cells and intestinal injury. The results showed that the expression of SOCS1 increased in CD patients, and the expression of SOCS1, p-p53 and PUMA increased in the mouse TNBS induced colitis model. Using IFN-γ treated HT-29 cells as an apoptotic model of intestinal epithelial cells in vitro, we confirmed that SOCS1 promoted apoptosis of intestinal epithelial cells by activating p53. In HT-29 cells which were treated with IFN-γ, the interaction between p53 and SOCS1 and phosphorylation of p53 were significantly higher than untreated cells. When knocking SOCS1 down by using SOCS1 siRNA, phosphorylation of p53 and apoptosis of intestinal epithelial cells which was induced by IFN-γ were significantly inhibited. In summary, our findings suggest that SOCS1 may promote apoptosis of intestinal epithelial cells at least partly through mediating p53 signaling.

• Authors: Xiaopeng Cui, Xiaohang Shan, Ji Qian, Qianqian Ji, Liang Wang, Xiaotong Wang, Manhua Li, Haifang Ding, Qingqing Liu, Lingling Chen, Dongmei Zhang, Runzhou Ni
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 101 Issue 1 Pg. 1-11 (08 2016) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 27236107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016. Published by Elsevier Inc.

Chemical References

• SOCS1 protein, human
• Socs1 protein, mouse
• Suppressor of Cytokine Signaling 1 Protein
• Tumor Suppressor Protein p53
• Interferon-gamma
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• Apoptosis (drug effects)
• Colitis
• Crohn Disease (metabolism, pathology)
• Epithelial Cells (drug effects, metabolism, pathology)
• Female
• Gene Knockdown Techniques
• HT29 Cells
• Humans
• Interferon-gamma (pharmacology)
• Intestines (pathology)
• Mice, Inbred BALB C
• Signal Transduction (drug effects)
• Suppressor of Cytokine Signaling 1 Protein (metabolism)
• Trinitrobenzenesulfonic Acid
• Tumor Suppressor Protein p53 (metabolism)