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Home > Protein Information

DR Promotes Intrahepatic Angiogenesis Through Slit2-Robo1 Signal

Catheter response (DR) is expanded in chronic liver disease and is related to the severity of the disease. In addition to its potential role in liver regeneration, DR also plays a role in promoting the wound healing response of peritubular fibrosis and inflammatory cell recruitment. However, there is no information about its role in intrahepatic angiogenesis. In the current study, the author investigated the potential role of DR cells in hepatic vascular remodeling during chronic liver disease.
Chronic liver injury drives wound healing response to maintain liver function and structural characteristics. The wound repair response activates the coordinated repair mechanisms of hepatocyte proliferation, extracellular matrix turnover and angiogenesis, and induces new angiogenesis and vascular system remodeling. In this context, the bile duct reaction (DR) expands to the regeneration reaction of the liver and maintains the reconstruction of the bile duct septum. DR cells are heterogeneous groups of bile cells, ranging from reactive bile duct cells to immature liver progenitor cells. The potential of bile duct septum to promote the regeneration of bile duct and parenchyma has been the focus of in-depth research in the field of liver disease. However, few studies have evaluated the interaction between DR cells and the surrounding environment and their role in liver wound repair response.
Patients with potential alcoholic liver disease (ARLD) and heavy alcohol consumption may develop alcoholic hepatitis (AH), which is an acute and chronic disease with poor short-term prognosis. It is characterized by inflammatory infiltration, fibrosis, hepatocyte damage and DR expansion, which is related to the severity of the disease and short-term mortality. The author recently described that in acute pancreatitis, DR cells showed a pro-inflammatory state, increased liver inflammation, and participated in neutrophil chemotaxis.
Gap ligands were initially described as secretory chemical reactants of growing axons and migrating neurons, which act through ROBO receptors. In recent years, it has been described that the guiding clues play a crucial role in angiogenesis, and the guiding clues are responsible for the development of neurons. Among these three gap proteins, Slit2 becomes an angiogenic factor by inducing the germination of new blood vessels in angiogenic tissues. Slit2 can play a positive and negative regulatory role on angiogenesis by combining with Robo1 or ROBO4 respectively. A study on skin and retina showed that the combination of Slit2 and Robo4 negatively regulates the formation of new blood vessels by inhibiting angiogenesis mediated by vascular endothelial growth factor (VEGF).
The potential angiogenic effect of Slit2 is mainly described in cancer and ischemic diseases. In these diseases, Slit2 secreted by solid tumors combines with Robo1 and is expressed in vascular endothelial cells to promote angiogenesis. On the contrary, tumor growth can be inhibited by blocking the activity of Robo1. Few studies have evaluated the role of Slit2-Robo1 axis in liver disease. In this respect, Slit2-Roo1 pathway is over-expressed in hepatocellular carcinoma, and the expression of Slit2 and Robo1 is enhanced in fibrotic liver, which promotes the formation of liver fibrosis by activating hepatic stellate cells. However, it is unclear whether Slit2-Roo1 pathway plays a role in promoting angiogenesis in liver regeneration and chronic liver injury.
In this study, the authors hypothesized that DR cells participate in liver tissue remodeling of ARLD. In order to determine the pathway of DR cell participation, the author analyzed the transcriptome of DR cells in a mouse model of chronic liver injury. The author found that liver angiogenesis is a significantly rich biological process related to DR cells. In addition, the author also studied the role of Slit2-Robo1 pathway in intrahepatic angiogenesis. The results show that DR cells promote liver angiogenesis, and Slit2-Robo1 pathway is the mechanism of this basic repair process.
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