Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis-Reference-Cited by-同舟云学术

Loss of apical sodium bile acid transporter alters bile acid circulation and reduces biliary damage in cholangitis

Published:2023-01-01 Issue:1 Volume:324 Page:G60-G77
ISSN:0193-1857
Container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology
language:en
Short-container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology

Author:

Meadows Vik¹^ORCID,Marakovits Corinn¹,Ekser Burcin²^ORCID,Kundu Debjyoti¹,Zhou Tianhao¹,Kyritsi Konstantina¹,Pham Linh¹,Chen Lixian¹,Kennedy Lindsey¹³^ORCID,Ceci Ludovica¹⁴,Wu Nan¹,Carpino Guido⁵,Zhang Wenjun²^ORCID,Isidan Abdulkadir²,Meyer Alison¹,Owen Travis¹,Gaudio Eugenio⁴,Onori Paolo⁴,Alpini Gianfranco¹³,Francis Heather¹³^ORCID

Affiliation:

1. Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana

2. Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana

3. Richard L. Roudebush Department of Veterans Affairs Medical Center, Indianapolis, Indiana

4. Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy

5. Department of Movement, Human and Health Sciences, University of Rome “Foro Italico,” Rome, Italy

Abstract

We evaluated knockdown of the apical sodium bile acid transporter (ASBT) using Vivo-Morpholino in Mdr2KO mice. ASBT inhibition decreases primary sclerosing cholangitis (PSC) pathogenesis by reducing hepatic mast cell infiltration, altering bile acid species/cholehepatic shunt, and regulating gut inflammation/dysbiosis. Since a large cohort of PSC patients present with IBD, this study is clinically important. We validated findings in human PSC and PSC-IBD along with studies in novel human 3-D organoids formed from human PSC livers.

Funder

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

HHS | NIH | National Institute on Alcohol Abuse and Alcoholism

U.S. Department of Veterans Affairs

School of Medicine, Indiana University

PSC Partners Seeking a Cure

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpgi.00112.2022