Yuefeng Ma1,2, Xiangwei Lv2, Jinjing He2, Tianqing Liu3, Shuang Wen3, Liming Wang2. 1. Department of General Surgery, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China. 2. Organ Transplantation Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, China. 3. Department of Pathology, Friendship Hospital of Dalian Medical University, Dalian, China.
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. METHODS: The livers of male Sprague-Dawley rats were reduced to approximately 50% and 30% of their original sizes and transplanted. A Wnt agonist (2-amino-4-[3,4-[methylenedioxy]benzylamino]-6-[3-methoxyphenyl] pyrimidine], 5 mg/kg bodyweight) or an equal volume of vehicle was administrated i.p. into the donor 1 h before the transplantation. Tissue and blood samples were collected at various times after transplantation, and a survival study was performed. 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.
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. METHODS: The livers of male Sprague-Dawley rats were reduced to approximately 50% and 30% of their original sizes and transplanted. A Wnt agonist (2-amino-4-[3,4-[methylenedioxy]benzylamino]-6-[3-methoxyphenyl] pyrimidine], 5 mg/kg bodyweight) or an equal volume of vehicle was administrated i.p. into the donor 1 h before the transplantation. Tissue and blood samples were collected at various times after transplantation, and a survival study was performed. 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.
Authors: E Koblihová; I Mrázová; Z Vaňourková; H Maxová; S Kikerlová; Z Husková; M Ryska; J Froněk; Z Vernerová Journal: Physiol Res Date: 2019-12-19 Impact factor: 1.881
Authors: Chad M Walesky; Kellie E Kolb; Carolyn L Winston; Jake Henderson; Benjamin Kruft; Ira Fleming; Sungjin Ko; Satdarshan P Monga; Florian Mueller; Udayan Apte; Alex K Shalek; Wolfram Goessling Journal: Nat Commun Date: 2020-11-19 Impact factor: 14.919