Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis.
Molecular markers of telomere dysfunction and senescence are common findings in the usual interstitial pneumonia pattern of lung fibrosis.
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DOI：
10.1111/his.14334
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发表时间：
2021-07
期刊：
影响因子：
6.4
通讯作者：
Wolters PJ
中科院分区：
文献类型：
--
作者：
Lee JS;La J;Aziz S;Dobrinskikh E;Brownell R;Jones KD;Achtar-Zadeh N;Green G;Elicker BM;Golden JA;Matthay MA;Kukreja J;Schwartz DA;Wolters PJ
特发性肺纤维化(IPF)是一种遗传介导的、与年龄相关的进行性肺纤维化，其病理特征为常见的间质性肺炎(UIP)纤维化模式。除IPF(非IPF UIP)的临床病程同样较差外，临床诊断的肺纤维化中也发现了UIP模式，这表明存在共同的分子驱动因素。对169例IPF患者和57例非IPF UIP患者的肺组织进行了组织病理学和分子生物学比较，以验证IPF患者和非IPF UIP患者是否具有共同的分子驱动因素。IPF和非IPF UIP患者的组织病理学改变都包括时间不均匀、显微镜下蜂窝样改变、成纤维细胞灶和致密的胶原纤维。非IPF UIP肺更易出现淋巴细胞浸润、非干酪性肉芽肿、以呼吸道为中心的炎症或小气道病变。与年龄相似的未使用供者对照相比，IPF和非IPF UIP肺的肺泡II型(AECII)细胞的端粒较短。IPF组和非IPF组UIP肺组织中衰老分子标志物(p16、p21)均升高。免疫染色定位这些蛋白在AECII细胞中的表达。IPF和非IPF UIP患者MUC5B启动子变异的小等位基因频率相似，MUC5B蛋白在IPF和非IPF UIP肺中的表达相似。端粒功能障碍和衰老的分子标志物在IPF和非IPF UIP肺中均有病理表达。这些发现表明，无论临床诊断如何，共同的分子驱动因素可能参与了UIP相关性肺纤维化的发病机制。
Idiopathic pulmonary fibrosis (IPF) is a genetically-mediated, age-associated, progressive form of pulmonary fibrosis characterized pathologically by a usual interstitial pneumonia (UIP) pattern of fibrosis. The UIP pattern is also found in pulmonary fibrosis attributable to clinical diagnoses other than IPF (Non-IPF UIP) whose clinical course is similarly poor, suggesting common molecular drivers. To test whether patients with IPF and non-IPF UIP share molecular drivers, lung tissue from 169 IPF patients and 57 non-IPF UIP patients were histopathologically and molecularly compared. Histopathologic changes in both IPF and non-IPF UIP patients included temporal heterogeneity, microscopic honeycombing, fibroblast foci and dense collagen fibrosis. Non-IPF UIP lungs were more likely to have lymphocytic infiltration, noncaseating granulomas, airway centered inflammation or small airways disease. Telomeres were shorter in alveolar type II (AECII) cells of both IPF and non-IPF UIP lungs compared to age-similar, unused donor, controls. Molecular markers of senescence (p16, p21) were elevated in lysates of IPF and non-IPF UIP lungs. Immunostaining localized expression of these proteins to AECII cells. The MUC5B promoter variant minor allele frequency was similar between IPF and non-IPF UIP patients and MUC5B protein expression was similar in IPF and non-IPF UIP lungs. Molecular markers of telomere dysfunction and senescence are pathologically expressed in both IPF and non-IPF UIP lungs. These findings suggest that common molecular drivers may contribute to the pathogenesis of UIP-associated pulmonary fibrosis, regardless of the clinical diagnosis.
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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.
DOI：
10.1056/nejmoa1801562
发表时间：
2018-12-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Juge PA;Lee JS;Ebstein E;Furukawa H;Dobrinskikh E;Gazal S;Kannengiesser C;Ottaviani S;Oka S;Tohma S;Tsuchiya N;Rojas-Serrano J;González-Pérez MI;Mejía M;Buendía-Roldán I;Falfán-Valencia R;Ambrocio-Ortiz E;Manali E;Papiris SA;Karageorgas T;Boumpas D;Antoniou K;van Moorsel CHM;van der Vis J;de Man YA;Grutters JC;Wang Y;Borie R;Wemeau-Stervinou L;Wallaert B;Flipo RM;Nunes H;Valeyre D;Saidenberg-Kermanac'h N;Boissier MC;Marchand-Adam S;Frazier A;Richette P;Allanore Y;Sibilia J;Dromer C;Richez C;Schaeverbeke T;Lioté H;Thabut G;Nathan N;Amselem S;Soubrier M;Cottin V;Clément A;Deane K;Walts AD;Fingerlin T;Fischer A;Ryu JH;Matteson EL;Niewold TB;Assayag D;Gross A;Wolters P;Schwarz MI;Holers M;Solomon JJ;Doyle T;Rosas IO;Blauwendraat C;Nalls MA;Debray MP;Boileau C;Crestani B;Schwartz DA;Dieudé P
通讯作者：
Dieudé P
影响因子：
9.6
作者：
Hou, Peter C.;Filbin, Michael R.;Shapiro, Nathan I.
通讯作者：
Shapiro, Nathan I.
DOI：
10.1164/rccm.200406-710st
发表时间：
2005-04-15
影响因子：
24.7
作者：
American Thoracic Society;European Respiratory Society
通讯作者：
European Respiratory Society
DOI：
10.1164/rccm.201406-1162oc
发表时间：
2015-02-15
影响因子：
24.7
作者：
Kropski, Jonathan A.;Pritchett, Jason M.;Blackwell, Timothy S.
通讯作者：
Blackwell, Timothy S.