Folate receptor-beta expression as a diagnostic target in human & rodent nonalcoholic steatohepatitis.

Toxicology and Applied Pharmacology
April D LakeNathan J Cherrington

Abstract

Nonalcoholic steatohepatitis (NASH) afflicts 20-36% of individuals with nonalcoholic fatty liver disease (NAFLD). A lipotoxic hepatic environment, altered innate immune signaling and inflammation are defining features of progression to NASH. Activated resident liver macrophages express folate receptor beta (FR-β) which may be an indicator of progression from steatosis to NASH. The goals of this study were to characterize FR-β protein expression in human NAFLD and rodent models of NASH, and demonstrate liver targeting of an FR-β imaging agent to the liver of a rodent NASH model using FR-β. Rat liver lysates from methionine choline deficient (MCD) fed rats, high fat diet (HFD) and methionine choline sufficient (MC+) rat controls were analyzed for hepatic FR-β protein. The FR-β-targeted agent, Etarfolatide was injected into MCD and MC + -fed C57BL/6 mice for efficient FastSPECT hepatic imaging. Additionally, FR-β expression across the stages of human NAFLD from normal to NASH was assessed. FastSPECT images show targeting of Etarfolatide to the liver of mice fed 8 weeks of MCD diet but not control-fed mice. The MCD rat model exhibited significantly increased protein expression of hepatic FR-β in contrast to HFD or normal samples. S...Continue Reading

Citations

Jul 12, 2020·Annals of the Rheumatic Diseases·Kamala VanarsaChandra Mohan

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