Activation of autophagy during normothermic machine perfusion of discarded livers is associated with improved hepatocellular function

Author:

Ohman Anders1,Raigani Siavash23ORCID,Santiago John C.1,Heaney Megan G.1,Boylan Joan M.1,Parry Nicola4,Carroll Cailah2,Baptista Sofia G.2,Uygun Korkut3,Gruppuso Philip A.1,Sanders Jennifer A.1,Yeh Heidi2

Affiliation:

1. Department of Pediatrics, Rhode Island Hospital and Brown University, Providence, Rhode Island

2. Division of Transplant Surgery, Massachusetts General Hospital, Boston, Massachusetts

3. Center for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

4. Section of Pathology, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts

Abstract

We demonstrate that ischemia-reperfusion injury occurs in all livers during NMP, though there are notable differences in gene expression between functional and nonfunctional livers. We further demonstrate that activation of the liver’s repair and homeostasis mechanisms through autophagy plays a vital role in the graft’s response to injury and may impact liver function. These findings indicate that liver autophagy might be a key therapeutic target for rehabilitating the function of severely injured or untransplantable livers.

Funder

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

HHS | NIH | National Institute of Environmental Health Sciences

National Science Foundation

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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