Ghrelin Receptor Blockade Restricts Hepatic Echinococcus granulosus Infection by Suppressing Host Cell Proliferation and Enhancing Fibrotic Encapsulation.

INTRODUCTION

Cystic echinococcosis (CE) is a parasitic liver disease caused by Echinococcus granulosus (E.g) infection, characterized by hepatic fibrosis and liver necrosis. Ghrelin and its receptor GHSR have been proven to regulate the progression of hepatic E.g infection, and GHSR knockout inhibits infection progression. Nevertheless, the specific regulatory mechanism remains poorly understood.

METHODS

In this study, mice with hepatic E.g infection were intraperitoneally injected with ghrelin protein and the GHSR antagonist [D-Lys3]-GHRP-6 for 90 days, and the related molecular and pathological indexes were detected and analyzed.

RESULTS

Compared with untreated E.g-infected mice, ghrelin treatment increased serum ghrelin level and upregulated hepatic and lesion-perilesional ghrelin/GHSR expression. Ghrelin further elevated the expression of proliferation markers (Ki67, PCNA, Cyclin D1 and Cyclin E1), inhibited the activation of the hepatic TGF-β1/Smad3 fibrotic pathway, reduced the levels of α-SMA, Collagen Ⅰ and Collagen Ⅲ, and ultimately promoted hepatic E.g infection progression. In contrast, [D-Lys3]-GHRP-6 intervention decreased serum ghrelin and hepatic ghrelin/GHSR levels, downregulated the expression of cell proliferation-related proteins, activated the TGF-β1/Smad3 fibrotic pathway, increased fibrotic protein expression, and effectively alleviated the progression of hepatic E.g infection.

CONCLUSION

The GHSR antagonist attenuates hepatic E.g infection progression by inhibiting hepatocellular proliferation and promoting hepatic fibrosis. GHSR antagonist has the potential to be a novel therapeutic target for CE treatment.