A novel maladaptive unfolded protein response as a mechanism for small bowel resection-induced liver injury

Author:

Steinberger Allie E.1ORCID,Tecos Maria E.2ORCID,Phelps Hannah M.1,Rubin Deborah C.3ORCID,Davidson Nicholas O.3,Guo Jun1,Warner Brad W.4ORCID

Affiliation:

1. Department of Surgery, Washington University School of Medicine, St. Louis, Missouri

2. Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska

3. Division of Gastroenterology, Department of Medicine, Washington University, St. Louis, Missouri

4. Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine, St. Louis Children’s Hospital, St. Louis, Missouri

Abstract

The unfolded protein response (UPR) is a complex signaling cascade that converges upon C/EBP-homologous protein (CHOP). Under conditions of chronic cellular stress, the UPR shifts from homeostatic to proapoptotic leading to inflammation and cell death. Here, we provide evidence that small bowel resection-induced liver injury and fibrosis are mediated by a maladaptive hepatic UPR. Low-fat diet, TUDCA treatment, and ileocecal resection rescued the hepatic phenotype and reversed the UPR pattern.

Funder

St. Louis Children's Hospital Foundation

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

HHS | NIH | National Heart, Lung, and Blood Institute

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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