Partial hepatectomy‑induced upregulation of SNHG12 promotes hepatocyte proliferation and liver regeneration

Abstract

Following partial hepatectomy (pH), the complex process of liver regeneration is initiated, which encompasses the synchronized induction of hepatocyte proliferation. Hepatocyte proliferation can be regulated by multiple stimuli, including long non-coding rnas (lncrnas) and Wnt/β-catenin signaling, although the underlying mechanism of lncrna/Wnt in liver regeneration remains unclear. in the present study, a liver regeneration-associated functional lncrna was identified, and its function was delineated in vitro and in vivo; lncrna small nucleolar rna host gene 12 (snHG12) was revealed to be upregulated at various time-points after 2/3 pH. the expression of snHG12 was also increased in normal liver cell lines treated with different concentrations of hepatocyte growth factor (HGF). Functionally, snHG12 enhanced hepatocyte proliferation in vitro and in vivo, and the liver/body weight ratio of snHG12-overexpressing mice was significantly higher than that of the control mice. overexpression of snHG12 promoted the activation of Wnt/β-catenin signaling in hepatocytes. Furthermore, specific inhibition of Wnt/β-catenin signaling significantly attenuated snHG12-induced hepatocyte proliferation and the affected liver/body weight ratio. collectively, the results of the present study indicated that snHG12 contributes to liver regeneration by activating Wnt/β-catenin signaling. therefore, drugs that regulate the SNHG12/Wnt axis may be beneficial for liver regeneration following pH.

Stem cell therapy and tissue engineering strategies using cell aggregates and decellularized scaffolds for the rescue of liver failure

“…Before cell transplantation for the treatment of inherited metabolic liver diseases, the host liver is often pre-treated to increase cell engraftment in vivo using a variety of strategies, such as partial hepatectomy, portal ligature/ embolization, or administration of chemotherapeutic drugs, which provide necessary stimuli for preparation of donor cell housing. [149][150][151][152] For instance, Pourcher et al 152 showed that cell engraftment was increased by around 3-folds after inducing volumetric portal embolization in the C57BL6 mice using polyester microspheres and subsequently injection of hepatocytes into the spleen.…”

Signaling pathways of liver regeneration: Biological mechanisms and implications

“… 108 , 109 , 110 Other studies have also demonstrated that certain genes act as the regulators of Wnt/β-catenin pathway, which accelerates hepatocyte growth and LR by regulating Wnt/β-catenin pathway. 111 , 112 Yin and Clemens et al. proved that Wnt/β-catenin pathway had a crucial effect on the initiation stage of LR from the opposite side, and reducing glycogen synthase kinase-3β (GSK-3β) phosphorylation affected the Wnt/β-catenin pathway, thereby inhibiting LR.…”

Therapeutic strategies to improve liver regeneration after hepatectomy

“…42,43 In mice receiving PHx, SNHG12 overexpression significantly increased PCNA-positive hepatocytes by stimulating Wnt/β-catenin signaling, whereas the liver regeneration promoted by SNHG overexpression was alleviated by Wnt inhibitor IWR-1. 44 Inhibition of factors that interfere with the cell cycle can also boost liver regeneration. As a cell cycle halter, p21 suppressed cell cycle progression in hepatocytes and impeded liver regeneration.…”