Nonalcoholic Steatohepatitis Promoting Kinases

Samar H. Ibrahim; Petra Hirsova; Harmeet Malhi; Gregory J. Gores

doi:10.1055/s-0040-1713115

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2020; 40(04): 346-357
DOI: 10.1055/s-0040-1713115

Review Article

Nonalcoholic Steatohepatitis Promoting Kinases

Samar H. Ibrahim

¹Division of Gastroenterology & Hepatology in the Department of Pediatrics, Medicine Mayo Clinic, Rochester, Minnesota

²Division of Gastroenterology & Hepatology in the Department of Medicine Mayo Clinic, Rochester, Minnesota

,

Petra Hirsova

²Division of Gastroenterology & Hepatology in the Department of Medicine Mayo Clinic, Rochester, Minnesota

,

Harmeet Malhi

²Division of Gastroenterology & Hepatology in the Department of Medicine Mayo Clinic, Rochester, Minnesota

,

Gregory J. Gores

²Division of Gastroenterology & Hepatology in the Department of Medicine Mayo Clinic, Rochester, Minnesota

› Author Affiliations

Abstract

Nonalcoholic hepatitis (NASH) is the progressive inflammatory form of nonalcoholic fatty liver disease. Although the mechanisms of hepatic inflammation in NASH remain incompletely understood, emerging literature implicates the proinflammatory environment created by toxic lipid-induced hepatocyte injury, termed lipotoxicity. Interestingly, numerous NASH-promoting kinases in hepatocytes, immune cells, and adipocytes are activated by the lipotoxic insult associated with obesity. In the current review, we discuss recent advances in NASH-promoting kinases as disease mediators and therapeutic targets. The focus of the review is mainly on the mitogen-activated protein kinases including mixed lineage kinase 3, apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase, and p38 MAPK; the endoplasmic reticulum (ER) stress kinases protein kinase RNA-like ER kinase and inositol-requiring protein-1α; as well as the Rho-associated protein kinase 1. We also discuss various pharmacological agents targeting these stress kinases in NASH that are under different phases of development.

Keywords

mitogen-activated protein kinases - Rho-associated protein kinase - endoplasmic reticulum stress - nonalcoholic steatohepatitis

Full Text

References

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