Inositol-Requiring Kinase 1 Regulates Apoptosis via Inducing Endoplasmic Reticulum Stress in Colitis Epithelial Cells
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ORIGINAL ARTICLE
Inositol‑Requiring Kinase 1 Regulates Apoptosis via Inducing Endoplasmic Reticulum Stress in Colitis Epithelial Cells Bei Zhang1 · XiaoYan Su2 · ZhengYuan Xie1 · Hao Ding1 · Ting Wang3 · RuYi Xie1 · ZhiLi Wen1 Received: 12 October 2019 / Accepted: 16 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Background Endoplasmic reticulum stress (ERS) has been studied as critical factor during occurrence and development of ulcerative colitis (UC). However, the role of ERS in inflamed UC remains unclear. Aims The purpose of this study was to analyze the role of inositol-requiring kinase 1 (IRE-1), a major regulator of ER, in regulating ERS and cell viability. Methods In UC mucosa tissue, IRE-1, BiP, XBP-1s, CHOP caspase-12 and GADD34 mRNA were assayed by qRT-PCR. Then, human normal colon epithelial cell line (NCM-460) and colon fibroblast cell line (CCD-33Co) were cultured, and downregulated or upregulated IRE-1 expression. ERS was induced with 100 ng/mL of Interleukin 6 (IL-6). CCK8 assay was performed to analyze cell proliferation. Flow cytometry analysis was conducted to detect the apoptosis. Western blot assay was used to examine ERS markers. Results IRE-1, BiP, XBP-1s, caspase-12 and CHOP mRNA were highly expressed in UC mucosa tissue, and the expression of GADD34 mRNA significantly decreased. These results show that ERS-induced unfolded protein response was enhanced in UC mucosa tissue. In cells, silencing the expression of IRE-1 could suppress cell proliferation and promote apoptosis through activating unfolded protein response, while the over-expression of IRE-1 had the opposite effect. IL-6 could induce ERS and cells apoptosis. Furthermore, we demonstrated that shRNA IRE-1 could enhance the inhibition of IL-6 on cells viability. Conclusions Inhibition of IRE-1 enhanced unfolded protein response and cells apoptosis and IL-6-induced ERS and suggested that IRE-1 might be a potential target of UC. Keywords Ulcerative colitis · Inositol-requiring kinase 1 · Interleukin 6 · Endoplasmic reticulum stress · Unfolded protein response · Apoptosis
* ZhiLi Wen [email protected]
RuYi Xie [email protected]
Bei Zhang [email protected]
1
The Department of Gastroenterology, Second Hospital Affiliated to Nanchang University, No. 1 Minde Road, Nanchang 330006, Jiangxi, People’s Republic of China
2
The Department of Pathology, Second Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China
3
The Department of Gastroenterology, First Hospital Affiliated to Nanchang University, Nanchang 330006, Jiangxi, People’s Republic of China
XiaoYan Su [email protected] ZhengYuan Xie [email protected] Hao Ding [email protected] Ting Wang [email protected]
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Introduction Ulcerative colitis (UC) and Crohn disease are the most common forms of inflammatory bowel disease (IBD). UC is a common, recurrent, and nonspecific chronic inflammation of the colon and is confined to the mucosa and submucosa
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