Wnt agonist stimulates liver regeneration after small‐for‐size liver transplantation in rats

Abstract

Aim: Liver regeneration is inhibited in small-for-size grafts, which plays a role in the failure of partial liver grafts after transplantation. The Wnt/β-catenin signaling pathway plays a critical role in liver development, regeneration and homeostasis. In this study, we investigated whether pharmacological activation of Wnt signaling improves liver regeneration after small-for-size liver transplantation. Tissue and blood samples were collected at various times after transplantation, and a survival study was performed. Methods:Results: Hepatic expression of active β-catenin and its downstream target gene Axin2 were decreased in 30% of liver grafts after transplantation while the Wnt agonist increased their expression similar to the 50% liver grafts. The Wnt agonist reversed inhibition of cyclin D1 expression and adenosine triphosphate production in the 30% liver grafts compared with the 50% grafts. The Wnt agonist also attenuated hepatocellular injury and increased the hepatocyte proliferation response, liver regeneration rate and survival after transplantation of the 30% liver graft.Conclusion: Activation of Wnt/β-catenin signaling in liver grafts by pharmacological pretreatment can accelerate regeneration in a partial liver transplant model.

The roles of Wnt/β‐catenin pathway in tissue development and regenerative medicine

“…In addition, activation of Wnt/β‐catenin pathway stimulated proliferation of hepatocytes (Gougelet & Colnot, ; Wang, Zhao, Fish, Logan, & Nusse, ), and the more quiescent liver progenitors (Yang et al, ), which often contributes toward liver regeneration (Saliani et al, ). Pre‐treatment with a Wnt/β‐catenin agonist activates the inhibited hepatocyte proliferation in the small‐for‐size rat liver graft model (Ma et al, ). It was also observed that Wnt/β‐catenin pathway can mediate the protection of the liver against oxidative injury by preserving mitochondrial functions (Karimaian, Majidinia, Bannazadeh Baghi, & Yousefi, ).…”

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

“…previous studies have widely reported that the Wnt/β-catenin pathway plays a primary role in organogenesis, homeostasis and various human diseases (29). in terms of liver regeneration, several studies have revealed the functional role of Wnt/β-catenin signaling; the literature demonstrated that the Wnt/β-catenin pathway is involved in Brahma-related gene 1-mediated liver regeneration (30), and there is direct evidence that Wnt agonists promote liver regeneration after small-for-size liver transplantation in vivo (31). Given that the interplay between the Wnt/β-catenin pathway and lncrnas has been reported in numerous diseases, including liver cancer, it is likely that snHG12 accelerates liver regeneration by activating Wnt signaling.…”

Pharmacological Stimulation of Wnt/ß-catenin Signaling Pathway Attenuates the Course of Thioacetamide-Induced Acute Liver Failure

“…0.5 ml). This dose of Wnt agonist was previously shown to effectively stimulate Wnt/β-catenin signaling pathway in the liver (Kuncewitch et al 2013, Ma et al 2016.…”

“…It has been established in embryological studies that 2-amino-4-[3,4-(methlylenedioxy)benzylamino]-6(3methoxyphenly)pyrimidine, a small-molecule pyrimidine derivative, is an agonist of Wnt signaling pathway (Kaldis andPagano 2009, Liu et al 2005) which was efficiently activated after its intraperitoneal (i.p.) administration (Kuncewitch et al 2013, Ma et al 2016. Therefore, we used here this Wnt agonist for time-limited stimulation of the pathway; this approach should minimize potential detrimental off-target effects of alternative permanent stimulation of the Wnt/β-catenin signaling pathway.…”