典型文献
Inhibition of ASCT2 induces hepatic stellate cell senescence with modified proinflammatory secretome through an IL-1α/NF-κB feedback pathway to inhibit liver fibrosis
文献摘要：
Senescence of activated hepatic stellate cells(aHSCs)is a stable growth arrest that is impli-cated in liver fibrosis regression.Senescent cells often accompanied by a multi-faceted senescence-asso-ciated secretory phenotype(SASP).But little is known about how alanine-serine-cysteine transporter type-2(ASCT2),a high affinity glutamine transporter,affects HSC senescence and SASP during liver fibrosis.Here,we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers.We first discovered ASCT2 inhibition induced HSCs to senes-cence in vitro and in vivo.The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration.Mechanically,ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP,interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82.From a translational perspective,atractylenolide Ⅲ is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2.The presence of-OH group in atractylenolide Ⅲ is sug-gested to be favorable for the inhibition of ASCT2.Importantly,atractylenolide Ⅲ could be utilized to treat liver fibrosis mice.Taken together,ASCT2 controlled HSC senescence while modifying the proin-flammatory SASP.Targeting ASCT2 by atractylenolide Ⅲ could be a therapeutic candidate for liver fibrosis.
文献关键词：
中图分类号：
作者姓名：
Feixia Wang;Zhanghao Li;Li Chen;Ting Yang;Baoyu Liang;Zili Zhang;Jiangjuan Shao;Xuefen Xu;Guoping Yin;Shijun Wang;Hai Ding;Feng Zhang;Shizhong Zheng
作者机构：
Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Department of Anesthesiology,Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine,Nanjing 210003,China;College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250035,China;Department of General Surgery,Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine,Nanjing 210003,China
文献出处：
引用格式：
[1]Feixia Wang;Zhanghao Li;Li Chen;Ting Yang;Baoyu Liang;Zili Zhang;Jiangjuan Shao;Xuefen Xu;Guoping Yin;Shijun Wang;Hai Ding;Feng Zhang;Shizhong Zheng-.Inhibition of ASCT2 induces hepatic stellate cell senescence with modified proinflammatory secretome through an IL-1α/NF-κB feedback pathway to inhibit liver fibrosis)[J].药学学报（英文版）,2022(09):3618-3638
A类：
aHSCs,Senescent,Lys82,atractylenolide,Asn230
B类：
Inhibition,ASCT2,induces,hepatic,stellate,senescence,modified,proinflammatory,secretome,through,feedback,pathway,fibrosis,Senescence,activated,cells,stable,growth,arrest,that,impli,cated,regression,often,accompanied,by,multi,faceted,asso,ciated,secretory,phenotype,SASP,But,little,known,about,how,alanine,serine,cysteine,transporter,high,affinity,glutamine,affects,during,Here,identified,mainly,elevated,positively,correlated,human,mouse,fibrotic,livers,We,first,discovered,inhibition,induced,vitro,vivo,were,restricted,initiation,prevent,paracrine,migration,Mechanically,was,target,glutaminolysis,dependent,interfering,loop,via,interacting,precursor,From,translational,perspective,inhibitor,directly,bound,presence,group,sug,gested,be,favorable,Importantly,could,utilized,treat,mice,Taken,together,controlled,while,modifying,Targeting,therapeutic,candidate
AB值：
0.498704
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