Non-coding RNAs(ncRNAs),encompassing microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),have emerged as critical regulators of gene expression and cellular function.In alcohol-associated liver...Non-coding RNAs(ncRNAs),encompassing microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),have emerged as critical regulators of gene expression and cellular function.In alcohol-associated liver disease(ALD),chronic alcohol consumption disrupts the expression and function of ncRNAs in the liver and circulation,contributing to the disease's pathogenesis and progression.Dysregulated ncRNAs influence key pathways involved in hepatocyte injury,lipid metabolism,inflammation,and hepatic stellate cell(HSC)activation,thereby exacerbating steatosis,inflammation,and fibrosis.Furthermore,extracellular vesicles play a pivotal role in mediating ncRNA-driven intercellular communication,amplifying liver damage and fibrosis.This review provides a comprehensive overview of the multifaceted roles of ncRNAs in ALD,with a focus on their mechanistic contributions to disease development and progression.Additionally,we discuss the potential of ncRNAs as diagnostic biomarkers and therapeutic targets,emphasizing their translational relevance in addressing the burden of ALD.展开更多
Alcohol-associated liver disease(ALD)is a growing global health concern and its prevalence and severity are increasing steadily.While bacterial endotoxin translocation into the portal circulation is a well-established...Alcohol-associated liver disease(ALD)is a growing global health concern and its prevalence and severity are increasing steadily.While bacterial endotoxin translocation into the portal circulation is a well-established key factor,recent evidence highlights the critical role of sterile inflammation,triggered by diverse stimuli,in alcohol-induced liver injury.This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD.It examines the contributions of both parenchymal cells,like hepatocytes,and non-parenchymal cells,such as hepatic stellate cells,Kupffer cells,neutrophils,and liver sinusoidal endothelial cells,in driving the progression of the disease.Additionally,we explored the involvement of key mediators,including cytokines,chemokines and inflammasomes,which regulate inflammatory responses and promote liver injury and fibrosis.A particular focus has been placed on extracellular vesicles(EVs)as essential mediators of intercellular communication both within and beyond the liver.These vesicles facilitate the transfer of signalling molecules,such as microRNAs and proteins,which modulate immune responses,fibrogenesis and lipid metabolism,thereby influencing disease progression.Moreover,we underscore the importance of organ-to-organ crosstalk,particularly in the gut-liver axis,where dysbiosis and increased intestinal permeability lead to microbial translocation,exacerbating hepatic inflammation.The adipose-liver axis is also highlighted,particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFC2304800 to Ge Zeng)NIH K99AA031067,the CSCTR Early Career Development Award,and Indiana Clinical and Translational Sciences Institute grant UM1TR004402(in part to Jing Ma)+3 种基金the National Institutes of Health(NIH R01AA030993 to Zhihong Yang)the American Liver Foundation Postdoctoral Award(in part to Themis Thoudam)NIH grant R01AA030312,Department of Veterans Affairs Merit Awards 1I01CX000361 and I01BX006202the Indiana University School of Medicine Dean's Scholar Award(in part to Suthat Liangpunsakul)。
文摘Non-coding RNAs(ncRNAs),encompassing microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs),have emerged as critical regulators of gene expression and cellular function.In alcohol-associated liver disease(ALD),chronic alcohol consumption disrupts the expression and function of ncRNAs in the liver and circulation,contributing to the disease's pathogenesis and progression.Dysregulated ncRNAs influence key pathways involved in hepatocyte injury,lipid metabolism,inflammation,and hepatic stellate cell(HSC)activation,thereby exacerbating steatosis,inflammation,and fibrosis.Furthermore,extracellular vesicles play a pivotal role in mediating ncRNA-driven intercellular communication,amplifying liver damage and fibrosis.This review provides a comprehensive overview of the multifaceted roles of ncRNAs in ALD,with a focus on their mechanistic contributions to disease development and progression.Additionally,we discuss the potential of ncRNAs as diagnostic biomarkers and therapeutic targets,emphasizing their translational relevance in addressing the burden of ALD.
基金supported by NIH grants K01AA26385,R01AA030993,Indiana University Research Support Fund Grant(IU RSFG),Indiana Institute for Medical Research(IIMR),the Ralph W.and Grace M.Showalter Research Trust and the Indiana University School of Medicine and the Central Society for Clinical and Translational Research(CSCTR)Early Career Development AwardJM is supported in part by NIH grant K99AA031067,the Indiana Clinical and Translational Sciences Institute grant UM1TR004402 and the CSCTR Early Career Development Award+2 种基金GZ is supported by Southern Medical UniversityTT is supported in part by the American Liver Foundation Postdoctoral awardSL is supported in part by NIH/NIAAA grants U01AA026917,UH2/UH3 AA026903,R01AA030312,Department of Veterans Affairs Merit Awards 1I01CX000361 and I01 BX006202 and Dean’s Scholar from the Indiana University School of Medicine.
文摘Alcohol-associated liver disease(ALD)is a growing global health concern and its prevalence and severity are increasing steadily.While bacterial endotoxin translocation into the portal circulation is a well-established key factor,recent evidence highlights the critical role of sterile inflammation,triggered by diverse stimuli,in alcohol-induced liver injury.This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD.It examines the contributions of both parenchymal cells,like hepatocytes,and non-parenchymal cells,such as hepatic stellate cells,Kupffer cells,neutrophils,and liver sinusoidal endothelial cells,in driving the progression of the disease.Additionally,we explored the involvement of key mediators,including cytokines,chemokines and inflammasomes,which regulate inflammatory responses and promote liver injury and fibrosis.A particular focus has been placed on extracellular vesicles(EVs)as essential mediators of intercellular communication both within and beyond the liver.These vesicles facilitate the transfer of signalling molecules,such as microRNAs and proteins,which modulate immune responses,fibrogenesis and lipid metabolism,thereby influencing disease progression.Moreover,we underscore the importance of organ-to-organ crosstalk,particularly in the gut-liver axis,where dysbiosis and increased intestinal permeability lead to microbial translocation,exacerbating hepatic inflammation.The adipose-liver axis is also highlighted,particularly the impact of adipokines and free fatty acids from adipose tissue on hepatic steatosis and inflammation in the context of alcohol consumption.
