2. Academic Validation
  3. Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells

Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells

  • Nat Commun. 2022 Jul 30;13(1):4428. doi: 10.1038/s41467-022-32158-7.
Dongke Xu  # 1,  Ruijun Ma  # 2,  Yi Ju 1,  Xiaowei Song 3,  Baolin Niu 1,  Wenting Hong 1,  Rong Wang 2,  Qin Yang 4,  Zhi Zhao 5,  Yuchen Zhang 1,  Yufan Zheng 1,  Qianming Bai 6,  Mingfang Lv 7,  Ning Sun 8 9,  Xiaobo Li 10
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 2 Center for Gastrointestinal Endoscopy, Shanxi Provincial People's Hospital, Taiyuan, China.
  • 3 Department of Chemistry, Fudan University, Shanghai, China.
  • 4 Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, China.
  • 5 Department of Medical Record and Statistics, Shanxi Provincial People's Hospital, Taiyuan, China.
  • 6 Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China.
  • 7 Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 8 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China. sunning@fudan.edu.cn.
  • 9 Wuxi School of Medicine, Jiangnan University, Jiangsu, China. sunning@fudan.edu.cn.
  • 10 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China. xbli@fudan.edu.cn.
  • # Contributed equally.
PMID: 35908039 DOI: 10.1038/s41467-022-32158-7
Abstract

Cholesterol sulfate, produced by hydroxysteroid sulfotransferase 2B1 (SULT2B1), is highly abundant in the intestine. Herein, we study the functional role and underlying intestinal epithelial repair mechanisms of Cholesterol sulfate in ulcerative colitis. The levels of Cholesterol and Cholesterol sulfate, as well as the expression of Sult2b1 and genes involved in Cholesterol biosynthesis, are significantly higher in inflamed tissues from patients with ulcerative colitis than in intestinal mucosa from healthy controls. Cholesterol sulfate in the gut and circulation is mainly catalyzed by intestinal epithelial SULT2B1. Specific deletion of the Sult2b1 gene in the intestinal epithelial cells aggravates dextran sulfate sodium-induced colitis; however, dietary supplementation with Cholesterol sulfate ameliorates this effect in acute and chronic ulcerative colitis in mice. Cholesterol sulfate promotes Cholesterol biosynthesis by binding to Niemann-Pick type C2 protein and activating sterol regulatory element binding protein 2 in colonic epithelial cells, thereby alleviates ulcerative colitis. In conclusion, Cholesterol sulfate contributes to the healing of the mucosal barrier and exhibits therapeutic efficacy against ulcerative colitis in mice.

Figures
Products