Divergent roles for Clusterin in Lung Injury and Repair.
Divergent roles for Clusterin in Lung Injury and Repair.
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DOI：
10.1038/s41598-017-15670-5
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发表时间：
2017-11-13
影响因子：
4.6
通讯作者：
Murray LA
中科院分区：
文献类型：
--
作者：
Habiel DM;Camelo A;Espindola M;Burwell T;Hanna R;Miranda E;Carruthers A;Bell M;Coelho AL;Liu H;Pilataxi F;Clarke L;Grant E;Lewis A;Moore B;Knight DA;Hogaboam CM;Murray LA
肺纤维化是以肺上皮细胞的丧失和异常功能为特征的未减弱的伤口愈合反应。在此，我们报道了细胞外促凋亡素促进上皮细胞凋亡，而细胞内促凋亡素在肺修复过程中维持上皮细胞的活力。与正常肺和COPD肺不同，IPF肺的特征在于细胞外白介素显著增加，而细胞内白介素明显相反。体外和体内研究表明，细胞外促凋亡素促进上皮细胞凋亡，而细胞间促凋亡素调节DNA修复蛋白，MSH 2，MSH 6，OGG 1和BRCA 1的表达。博莱霉素治疗后，白细胞蝶呤缺乏（CLU-/-）小鼠的纤维化反应持续存在，并与DNA损伤增加、DNA修复反应减少和细胞衰老增加相关。值得注意的是，这种模式反映了在IPF肺组织中观察到的模式。总之，我们的结果表明，在纤维化过程中，白藜芦醇的细胞定位导致对上皮细胞再生和肺修复的不同影响。
Lung fibrosis is an unabated wound healing response characterized by the loss and aberrant function of lung epithelial cells. Herein, we report that extracellular Clusterin promoted epithelial cell apoptosis whereas intracellular Clusterin maintained epithelium viability during lung repair. Unlike normal and COPD lungs, IPF lungs were characterized by significantly increased extracellular Clusterin whereas the inverse was evident for intracellular Clusterin. In vitro and in vivo studies demonstrated that extracellular Clusterin promoted epithelial cell apoptosis while intercellular Clusterin modulated the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1. The fibrotic response in Clusterin deficient (CLU−/−) mice persisted after bleomycin and it was associated with increased DNA damage, reduced DNA repair responses, and elevated cellular senescence. Remarkably, this pattern mirrored that observed in IPF lung tissues. Together, our results show that cellular localization of Clusterin leads to divergent effects on epithelial cell regeneration and lung repair during fibrosis.
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影响因子：
3.7
作者：
Murray LA;Rosada R;Moreira AP;Joshi A;Kramer MS;Hesson DP;Argentieri RL;Mathai S;Gulati M;Herzog EL;Hogaboam CM
通讯作者：
Hogaboam CM
影响因子：
30.8
作者：
Fingerlin, Tasha E.;Murphy, Elissa;Zhang, Weiming;Peljto, Anna L.;Brown, Kevin K.;Steele, Mark P.;Loyd, James E.;Cosgrove, Gregory P.;Lynch, David;Groshong, Steve;Collard, Harold R.;Wolters, Paul J.;Bradford, Williamson Z.;Kossen, Karl;Seiwert, Scott D.;du Bois, Roland M.;Garcia, Christine Kim;Devine, Megan S.;Gudmundsson, Gunnar;Isaksson, Helgi J.;Kaminski, Naftali;Zhang, Yingze;Gibson, Kevin F.;Lancaster, Lisa H.;Cogan, Joy D.;Mason, Wendi R.;Maher, Toby M.;Molyneaux, Philip L.;Wells, Athol U.;Moffatt, Miriam F.;Selman, Moises;Pardo, Annie;Kim, Dong Soon;Crapo, James D.;Make, Barry J.;Regan, Elizabeth A.;Walek, Dinesha S.;Daniel, Jerry J.;Kamatani, Yoichiro;Zelenika, Diana;Smith, Keith;McKean, David;Pedersen, Brent S.;Talbert, Janet;Kidd, Raven N.;Markin, Cheryl R.;Beckman, Kenneth B.;Lathrop, Mark;Schwarz, Marvin I.;Schwartz, David A.
通讯作者：
Schwartz, David A.
影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
影响因子：
5.9
作者：
Kwon, Hyouk-Soo;Kim, Tae-Bum;Cho, You Sook
通讯作者：
Cho, You Sook
DOI：
10.1165/rcmb.2012-0030oc
发表时间：
2012-10-01
影响因子：
6.4
作者：
Chen, Leiling;Acciani, Thomas;Perl, Anne-Karina T.
通讯作者：
Perl, Anne-Karina T.