Ghrelin is involved in regulating the progression of Echinococcus Granulosus-infected liver lesions through suppression of immunoinflammation and fibrosis

作者：Jiang Zhu, Hongqiong Zhao, Aili Aierken, Tanfang Zhou, Meng Menggen, Huijing Gao, Rongdong He, Kalibixiati Aimulajiang, Hao Wen · 发表于：PLoS neglected tropical diseases · 年份：2024 · DOI：10.1371/journal.pntd.0012587 · 被引用次数：9 · 研究领域：Parasitic infections in humans and animals、Neuroscience of respiration and sleep、Genetic and Kidney Cyst Diseases

BACKGROUND: Cystic Echinococcosis (CE) is a zoonotic disease causing fibrosis and necrosis of diseased livers caused by infection with Echinococcus granulosus (E.g). There is evidence that E.g is susceptible to immune escape and tolerance when host expression of immunoinflammation and fibrosis is suppressed, accelerating the progression of CE. Ghrelin has the effect of suppressing immunoinflammation and fibrosis, and whether it is involved in regulating the progression of E.g-infected liver lesions is not clear. METHODS: Serum and hepatic Ghrelin levels were observed in E.g-infected mice (4, 12 and 36 weeks) and compared with healthy control groups. Co-localization analysis is performed between protein expression of Ghrelin in and around the hepatic lesions of E.g-infected 12-week mice and protein expression of different hepatic histiocytes by mIHC. HepG2 cells and protoscoleces (PSCs) protein were co-cultured in vitro, as well as PSCs were alone in vitro, followed by exogenously administered of Ghrelin and its receptor blocker, [D-Lys3]-GHRP-6, to assess their regulatory effects on immunoinflammation, fibrosis and survival rate of PSCs. RESULTS: Serum Ghrelin levels were increased in E.g-infected 4- and 12-week mice, and reduced in 36-week mice. E.g-infected mice consistently recruited Ghrelin in and around the hepatic lesions, which was extremely strongly co-localized with the protein expression of hepatic stellate cells (HSCs), T cells and the TGF-β1/Smad3 pathway. The sec...