Upregulation of C-Reactive Protein by Placenta-Derived Mesenchymal Stem Cells Promotes Angiogenesis in A Rat Model with Cirrhotic Liver

Int J Stem Cells. 2020 Nov 30;13(3):404-413. doi: 10.15283/ijsc20052.


Background and objectives: Liver cirrhosis is accompanied by abnormal vascular shunts. The Wnt pathway is essential for endothelial cell survival and proliferation. C-reactive protein (CRP), which is produced by hepatocyte, activates angiogenesis in cardiovascular diseases.

Methods and results: The expression of CRP in CCl4-injured rat livers was detected using qRT-PCR and Western blotting after transplantation of placenta-derived mesenchymal stem cells (PD-MSCs) into rats. To determine whether CRP functions in hepatic regeneration by promoting angiogenesis through the Wnt pathway, we detected VEGF and β-catenin in liver tissues and BrdU and β-catenin in hepatocytes by immunofluorescence. The expression levels of CRP, Wnt pathway-related and angiogenic factors were increased in CCl4-injured and PD-MSCs transplanted rat livers. In vitro, the expression levels of Wnt signaling and angiogenic factors were decreased in siRNA-CRP-transfected rat hepatocytes.

Conclusions: CRP upregulation by PD-MSCs participates in vascular remodeling to promote liver regeneration via the Wnt signaling pathway during hepatic failure.

Keywords: C-reactive protein; Liver cirrhosis; Placenta-derived mesenchymal stem cells; Vascular remodeling; Wnt pathway.