典型文献
Hepatocyte-derived VEGFA accelerates the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via activating hepatic stellate cells
文献摘要：
Non-alcoholic fatty liver disease(NAFLD)is emerging as an epidemic risk factor for hepatocellular carcinoma(HCC).The progression of NAFLD to HCC is closely associated with paracrine communication among hepatic cells.Vascular endothelial growth factor A(VEGFA)plays a key role in NAFLD and HCC;however,the cellular communication of VEGFA in the pathological transition from NAFLD to HCC remains unclear.Here,we found that VEGFA elevation was considerably distributed in hepatocytes of clinical and murine NAFLD-HCC specimens.Notably,progression from NAFLD to HCC was attenuated in hepatocyte-specific deletion of Vegfa(VegfaAhep)mice.Mechanistically,VEGFA activated human hepatic stellate cell(HSC)LX2 into a fibrogenic phenotype via VEGF-VEGFR signaling in fatty acid medium,and HSC activation was largely attenuated in Vegfa△hep mice during NAFLD-HCC progression.Additionally,a positive correlation between VEGFA and hepatic fibrosis was observed in the NAFLD-HCC cohort,but not in the HBV-HCC cohort.Moreover,LX2 cells could be activated by conditioned medium from NAFLD-derived organoids,but not from HBV livers,whereas this activation was blocked by a VEGFA antibody.In summary,our findings reveal that hepatocyte-derived VEGFA contributes to NAFLD-HCC development by activating HSCs and highlight the potential of precisely targeting hepatocytic VEGFA as a promising therapeutic strategy for NAFLD-HCC.
文献关键词：
中图分类号：
作者姓名：
Hao Shen;Han Yu;Qian-yu Li;Ya-ting Wei;Jing Fu;Hui Dong;Dan Cao;Lin-na Guo;Lei Chen;Yuan Yang;Ying Xu;Meng-chao Wu;Hong-yang Wang;Yao Chen
作者机构：
International Cooperation Laboratory on Signal Transduction,National Center for Liver Cancer,Ministry of Education Key Laboratory on signaling Regulation and Targeting Therapy of Liver Cancer,Shanghai Key Laboratory of Hepato-biliary Tumor Biology,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University/NAVAL Medical University,Shanghai 200433,China;Department of Pathology,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072,China;Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200438,China;Third Department of Hepatic Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai 200433,China
文献出处：
引用格式：
[1]Hao Shen;Han Yu;Qian-yu Li;Ya-ting Wei;Jing Fu;Hui Dong;Dan Cao;Lin-na Guo;Lei Chen;Yuan Yang;Ying Xu;Meng-chao Wu;Hong-yang Wang;Yao Chen-.Hepatocyte-derived VEGFA accelerates the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via activating hepatic stellate cells)[J].中国药理学报（英文版）,2022(11):2917-2928
A类：
Vegfa,VegfaAhep,hepatocytic
B类：
Hepatocyte,derived,VEGFA,accelerates,progression,alcoholic,fatty,disease,hepatocellular,carcinoma,via,activating,hepatic,stellate,cells,Non,NAFLD,emerging,epidemic,risk,HCC,closely,associated,paracrine,communication,among,Vascular,endothelial,growth,plays,key,role,however,pathological,transition,from,remains,unclear,Here,found,that,elevation,was,considerably,distributed,hepatocytes,clinical,murine,specimens,Notably,attenuated,specific,deletion,mice,Mechanistically,activated,human,LX2,into,fibrogenic,phenotype,VEGFR,signaling,acid,medium,activation,largely,during,Additionally,positive,correlation,between,fibrosis,observed,cohort,HBV,Moreover,could,by,conditioned,organoids,livers,whereas,this,blocked,antibody,In,summary,our,findings,reveal,contributes,development,HSCs,highlight,potential,precisely,targeting,promising,therapeutic,strategy
AB值：
0.495407
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
