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

ABSTRACT: INTRODUCTION: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-?) which may be an indicator of progression from steatosis to NASH. The goals of this study were to characterize FR-? protein expression in human NAFLD and rodent models of NASH, and demonstrate liver targeting of an FR-? imaging agent to the liver of a rodent NASH model using FR-?. METHODS: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-? protein. The FR-?-targeted agent, Etarfolatide was injected into MCD and MC?+?-fed C57BL/6 mice for efficient FastSPECT hepatic imaging. Additionally, FR-? expression across the stages of human NAFLD from normal to NASH was assessed. RESULTS: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-? in contrast to HFD or normal samples. Similarly human liver samples categorized as NASH Fatty or NASH Not Fatty showed elevated FR-? protein when compared to normal liver. FR-? transcript expression levels were elevated across both NASH Fatty and NASH Not Fatty samples. CONCLUSION:The findings in this study indicate that FR-? expression in NASH may be harnessed to target agents directly to the liver.

SUBMITTER: Lake AD 

PROVIDER: S-EPMC6487882 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature