C1q/tumor necrosis factor-related protein-3 acts as a target treating hepatic fibrosis

B.-R. Sun, H.-Y. Li, G.-P. Wang, Q.-A. Jia, C. Zhang

Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China. zhangchun0591@126.com

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• Oncology

OBJECTIVE: C1q/tumor necrosis factor-related protein-3 (CTRP3) is demonstrated as a crucial factor that participated in various fibrotic diseases. Activation of hepatic stellate cell in liver takes a critical effect on the pathogenesis of hepatic fibrosis. However, the role of CTRP3 in hepatic fibrosis remains elusive. Our present study aimed to explore the molecular mechanism of CTRP3 in fibroblast activation and the development of hepatic fibrosis.

MATERIALS AND METHODS: We carried out overexpression (OE) of CTRP3 or knockout (KO) of CTRP3 in hepatic stellate cells (HSCs), respectively. Then, transforming growth factor-beta (TGF-β) was used to stimulate HSCs activation. Adult male C57BL/6J mice were treated tetrachloromethane by intraperitoneal injection and mice injected saline were served as control. Recombinant CTRP3 (RC-CTRP3) was employed to treat CCl4-induced liver fibrosis. Then, the expression of fibrotic biomarkers, Notch signaling pathway-associated factors, liver histology and liver function were investigated in vivo, respectively.

RESULTS: Our results showed that CTRP3 decreased in fibrotic liver and TGF-β treated HSCs. In vitro, CTRP3 inhibited the activation of HSCs and impeded extracellular matrix (ECM) including collagen I and fibronectin via inhibiting Notch-1/Jagged-1 signaling pathway. In vivo, the indexes of fibrogenesis in liver fibrotic mice received RC-CTRP3 were mitigated via regulation of Notch-1/Jagged-1 signaling pathway. Moreover, liver histology and liver function were improved through the increase of CTRP3 level.

CONCLUSIONS: The results proved that CTRP3 as a distinguished anti-fibrotic target inhibited HSCs activation by TGF-β inducement and protected the liver tissue in the process of liver fibrosis.

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