Platelet activation relieves liver portal hypertension via the lymphatic system though the classical vascular endothelial growth factor receptor 3 signaling pathway  

作　　者：Min Chen Jin-Bo Zhao Guang-Bo Wu Zheng-Hao Wu Gu-Qing Luo Zhi-Feng Zhao Chi-Hao Zhang Jia-Yun Lin Hong-Jie Li Xiao-Liang Qi Hai-Zhong Huo Abudukadier Tuersun Qiang Fan Lei Zheng Meng Luo 

机构地区：[1]Department of General Surgery,Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University,School of Medicine,Shanghai Jiao Tong University,Shanghai 200011,China [2]Department of Urology,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China [3]Xijing Hospital of Digestive Diseases,Air Force Military Medical University,Xi’an 710032,Shaanxi Province,China

出　　处：《World Journal of Gastroenterology》2025年第10期86-102,共17页世界胃肠病学杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.82100639,No.82200630,and No.81970526;Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.202401023;Clinical Research Program of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.JYLJ202124;Shanghai Municipal Commission of Health and Family Planning,No.20244Y0195 and No.20234Y0132;the Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.JYZZ162;Science Foundation of Xinjiang Uygur Natural Autonomous Region,No.2022D01F17.

摘　　要：BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.

关 键 词：Portal hypertension CIRRHOSIS LYMPHANGIOGENESIS PLATELETS Vascular endothelial growth factor C 

分 类 号：R73[医药卫生—肿瘤]