Dong XQ, Zhang YH, Luo J, Li MJ, Ma LQ, Qi YT, Miao YL. Keratin 1 modulates intestinal barrier and immune response via kallikrein kinin system in ulcerative colitis. World J Gastroenterol 2025; 31(6): 102070 [PMID: 39958441 DOI: 10.3748/wjg.v31.i6.102070]
Corresponding Author of This Article
Ying-Lei Miao, Doctor, Chief Physician, Professor, Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, No. 295 Xichang Road, Wuhua District, Kunming 650032, Yunnan Province, China. miaoyinglei@yeah.net
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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Dong XQ, Zhang YH, Luo J, Li MJ, Ma LQ, Qi YT, Miao YL. Keratin 1 modulates intestinal barrier and immune response via kallikrein kinin system in ulcerative colitis. World J Gastroenterol 2025; 31(6): 102070 [PMID: 39958441 DOI: 10.3748/wjg.v31.i6.102070]
Xiang-Qian Dong, Juan Luo, Mao-Juan Li, Lan-Qing Ma, Ya-Ting Qi, Ying-Lei Miao, Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming 650032, Yunnan Province, China
Ying-Hui Zhang, Department of Gastroenterology, Affiliated Hospital of Yunnan University, Kunming 650021, Yunnan Province, China
Co-first authors: Xiang-Qian Dong and Ying-Hui Zhang.
Author contributions: Dong XQ and Miao YL contributed to the study design and manuscript revision; Zhang YH and Luo J were responsible for mice feeding and colon collection; Li MJ and Zhang YH carried out the experimental procedures; Ma LQ and Qi YT conducted the data analysis; Dong XQ and Zhang YH participated in manuscript writing and revision; Miao YL participated in manuscript editing; All authors have read and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 82160113; the “Xingdian Talents” Support Project of Yunnan Province, No. RLMY20220007; the Yunnan Province Clinical Research Center for Digestive Diseases, No. 202102AA100062; and the Applied Basic Research Projects of Yunnan Province, No. 2019FE001-039.
Institutional review board statement: This study does not involve any human experiments.
Institutional animal care and use committee statement: The animal experiments were approved by the Ethics Committee of Kunming Medical University, No. SCXK (Dian) K2020-0006, Date of approval: February 9, 2021.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: Ying-Lei Miao, Doctor, Chief Physician, Professor, Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, No. 295 Xichang Road, Wuhua District, Kunming 650032, Yunnan Province, China. miaoyinglei@yeah.net
Received: October 8, 2024 Revised: December 6, 2024 Accepted: December 19, 2024 Published online: February 14, 2025 Processing time: 94 Days and 0.6 Hours
Abstract
BACKGROUND
External factors in ulcerative colitis (UC) exacerbate colonic epithelial permeability and inflammatory responses. Keratin 1 (KRT1) is crucial in regulating these alterations, but its specific role in the progression of UC remains to be fully elucidated.
AIM
To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC.
METHODS
A KRT1 antibody concentration gradient test, along with a dextran sulfate sodium (DSS)-induced animal model, was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system (KKS) and the cleavage of bradykinin (BK)/high molecular weight kininogen (HK) in UC.
RESULTS
Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation, induced apoptosis, reduced HK expression, and increased BK expression. It further downregulated intestinal barrier proteins, including occludin, zonula occludens-1, and claudin, and negatively impacted the coagulation factor XII. These changes led to enhanced activation of BK and HK cleavage, thereby intensifying KKS-mediated inflammation in UC. In the DSS-induced mouse model, administration of KRT1 antibody mitigated colonic injury, increased colon length, alleviated weight loss, and suppressed inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-α. It also facilitated repair of the intestinal barrier, reducing DSS-induced injury.
CONCLUSION
KRT1 inhibits BK expression, suppresses inflammatory cytokines, and enhances markers of intestinal barrier function, thus ameliorating colonic damage and maintaining barrier integrity. KRT1 is a viable therapeutic target for UC.
Core Tip: Keratin 1 (KRT1) plays a protective role in ulcerative colitis by modulating the kallikrein kinin system and reducing inflammation. KRT1 enhances intestinal barrier function, inhibits inflammatory cytokines, and preserves colon integrity, positioning it as a potential therapeutic target for ulcerative colitis.
