Abstract
Liver regeneration is a complicated biological process orchestrated by various liver resident cells. Hepatic cell proliferation and reconstruction of the hepatic architecture involve multiple signaling pathways. It has been reported that the Hh signal is involved in liver regeneration. However, the signal transduction pathways and cell types involved are ill studied. This study aimed to investigate hedgehog signal response cell types and the specific molecular mechanism involved in the process of liver regeneration. Partial hepatectomy (PH) of 70% was performed on ICR (Institute of Cancer Research) mice to study the process of liver regeneration. We found that the hedgehog signal was activated significantly after PH, including hedgehog ligands, receptors and intracellular signaling molecules. Ligand signals were mainly expressed in bile duct cells and non-parenchymal hepatic cells, while receptors were expressed in hepatocytes and some non-parenchymal cells. Inhibition of the hedgehog signal treated with vismodegib reduced the liver regeneration rate after partial hepatectomy, including inhibition of hepatic cell proliferation by decreasing Cyclin D expression and disturbing the cell cycle through the accumulation of Cyclin B. The current study reveals the important role of the hedgehog signal and its participation in the regulation of hepatic cell proliferation and the cell cycle during liver regeneration. It provides new insight into the recovery of the liver after liver resection.
Highlights
The liver is a special organ with a strong ability to regenerate
To investigate the changes in the Hh signal in the process of liver regeneration, 70% partial hepatectomy was performed on ICR mice, and liver tissue samples were collected at different time points (1, 2, 3 and 7 days)
Our present study demonstrates that Hh signaling mediates liver regeneration through regulating DNA replication and cell division
Summary
The liver is a special organ with a strong ability to regenerate. After partial hepatectomy (PH), the liver can recover its original mass within two weeks [1]. Liver regeneration is a very complicated process that requires stages of initiation, proliferation and termination. Many studies have shown that cell proliferation during liver regeneration peaks at about 48 h post-PH, which involves the replication of mature hepatocytes [2,8]. Recent studies have indicated that hedgehog (Hh) signaling plays an important role in many types of chronic liver injury, and even in hepatocellular carcinoma [10,11,12,13,14]. In the process of liver fibrosis, Hh signaling could be activated in hepatic stellate cells (HSCs), promoting further activation and proliferation of HSCs, leading to fibrogenesis [15,16,17]. HSCs were considered as epithelial progenitors in the liver [18]
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