title: Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1-mediated mitochondrial fission.
abstract: Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.
authors.affiliation: Medicine Research Center, Binzhou Medical University, Yantai, China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Xu
authors.affiliation: School of Special Education, Binzhou Medical University, Yantai, China.
authors.forename: Youlei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Clinical Laboratory, Affiliated Hospital to Binzhou Medical University, Yantai, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Yantai, China.
authors.forename: Shengcui
authors.initials: S
authors.lastname: Lin
authors.affiliation: Medicine Research Center, Binzhou Medical University, Yantai, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Mao
authors.affiliation: Medicine Research Center, Binzhou Medical University, Yantai, China.
authors.forename: Bingsi
authors.initials: B
authors.lastname: Wang
authors.affiliation: Medicine Research Center, Binzhou Medical University, Yantai, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Song
authors.affiliation: Medicine Research Center, Binzhou Medical University, Yantai, China.|Department of Respiratory Medicine, Affiliated Hospital to Binzhou Medical University, Binzhou, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000378:metabolism*; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D024341:Xanthophylls / Q000494:pharmacology / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D024341:Xanthophylls; D051028:bcl-2-Associated X Protein; C005948:astaxanthine; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
keywords: astaxanthin; mitochondrial fission; myofibroblast apoptosis; pulmonary fibrosis