典型文献
The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration
文献摘要：
The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury.Pulmonary fibrosis(PF)is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells.In this study,we report that P21 expres-sion was increased in alveolar epithelial type 2 cells(AEC2s)in a time-dependent manner following mul-tiple bleomycin-induced PF.Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence.AEC2s with elevated expression of P21 lost their self-renewal and dif-ferentiation abilities.In particular,elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin inter-action.Meanwhile,senescent AEC2s triggered myofibroblast activation by releasing profibrotic cyto-kines.Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF.The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development,which suggests a potential strategy for the treatment of fibrotic lung diseases.
文献关键词：
中图分类号：
作者姓名：
Xiaoxi Lv;Chang Liu;Shanshan Liu;Yunxuan Li;Wanyu Wang;Ke Li;Fang Hua;Bing Cui;Xiaowei Zhang;Jiaojiao Yu;Jinmei Yu;ZhuoWei Hu
作者机构：
Immunology and Cancer Pharmacology Group,State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China;Drug Clinical Trial Institution,Children's Hospital,Capital Institute of Pediatrics,Beijing 100020,China;Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China
文献出处：
引用格式：
[1]Xiaoxi Lv;Chang Liu;Shanshan Liu;Yunxuan Li;Wanyu Wang;Ke Li;Fang Hua;Bing Cui;Xiaowei Zhang;Jiaojiao Yu;Jinmei Yu;ZhuoWei Hu-.The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration)[J].药学学报（英文版）,2022(02):735-746
A类：
AEC2s,AEC2,kines
B类：
cycle,inhibitor,P21,promotes,development,pulmonary,fibrosis,by,suppressing,lung,alveolar,regeneration,has,been,implicated,senescence,plays,important,role,injury,repair,process,following,Pulmonary,PF,disorder,characterized,epithelial,cells,In,this,study,we,report,that,was,increased,type,dependent,manner,mul,tiple,bleomycin,induced,Repeated,resulted,telomere,shortening,triggered,elevated,expression,lost,their,self,renewal,abilities,particular,not,only,arrest,but,also,bound,P300,catenin,inhibited,differentiation,disturbing,inter,action,Meanwhile,senescent,myofibroblast,activation,releasing,profibrotic,cyto,Knockdown,restored,mediated,mice,chronic,results,our,reveal,mechanism,failure,during,which,suggests,potential,strategy,treatment,diseases
AB值：
0.521955
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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。
