Mucus Hypersecretion and Ciliary Impairment in Conducting Airway Contribute to Alveolar Mucus Plugging in Idiopathic Pulmonary Fibrosis.
Mucus Hypersecretion and Ciliary Impairment in Conducting Airway Contribute to Alveolar Mucus Plugging in Idiopathic Pulmonary Fibrosis.
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气道传导中的粘液分泌过多和纤毛损伤导致特发性肺纤维化中的肺泡粘液堵塞
DOI：
10.3389/fcell.2021.810842
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhong NS
中科院分区：
文献类型：
--
作者：
Peng Y;Wang ZN;Xu AR;Fang ZF;Chen SY;Hou XT;Zhou ZQ;Lin HM;Xie JX;Tang XX;Wang DY;Zhong NS
特发性肺纤维化（IPF）是一种慢性肺部疾病，归因于遗传和环境风险的复杂相互作用。粘液纤毛清除 (MCC) 系统在维持空气进出肺泡的管道方面发挥着关键作用，但目前尚不清楚传导气道的 MCC 异常是否与 IPF 发病机制有关。在这项研究中，我们获得了 31 名 IPF 患者和 39 名对照受试者手术切除的支气管和周围肺组织，并通过免疫染色、扫描和透射电子显微镜探讨了 MCC 传导气道的形态特征。在支气管粘膜下区域，我们发现 IPF 患者的粘液腺 (MUC5B+) 面积显着大于对照组 (p < 0.05)。在三个气道区域（支气管、近端细支气管和远端细支气管）的表面上皮中，与对照组相比，IPF患者观察到分泌细胞MUC5B和MUC5AC表达增加，纤毛细胞数量减少，纤毛长度增加（均p < 0.05）。此外，IPF患者支气管和外周肺中MUC5B mRNA表达水平均高于对照组（p < 0.05），且93.55%的IPF受试者肺泡区有明显的MUC5B+粘液栓。在 IPF 患者和对照受试者中均未检测到 MUC5B rs35705950 单核苷酸多态性等位基因。我们的研究表明，粘液分泌过多和纤毛传导气道受损是肺泡区粘液堵塞的主要原因，可能与IPF患者的肺泡损伤密切相关。
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease attributed to the complex interplay of genetic and environmental risks. The muco-ciliary clearance (MCC) system plays a critical role in maintaining the conduit for air to and from the alveoli, but it remains poorly understood whether the MCC abnormalities in conducting airway are involved in IPF pathogenesis. In this study, we obtained the surgically resected bronchi and peripheral lung tissues from 31 IPF patients and 39 control subjects, and we sought to explore the morphologic characteristics of MCC in conducting airway by using immunostaining and scanning and transmission electron microscopy. In the submucosal regions of the bronchi, we found that the areas of mucus glands (MUC5B+) were significantly larger in IPF patients as compared with control subjects (p < 0.05). In the surface epithelium of three airway regions (bronchi, proximal bronchioles, and distal bronchioles), increased MUC5B and MUC5AC expression of secretory cells, decreased number of ciliated cells, and increased ciliary length were observed in IPF patients than control subjects (all p < 0.05). In addition, the mRNA expression levels of MUC5B were up-regulated in both the bronchi and peripheral lung of IPF patients than those of control subjects (p < 0.05), accompanied with 93.55% IPF subjects who had obvious MUC5B+ mucus plugs in alveolar regions. No MUC5B rs35705950 single-nucleotide polymorphism allele was detected in both IPF patients and control subjects. Our study shows that mucus hypersecretion and ciliary impairment in conducting airway are major causes of mucus plugs in alveolar regions and may be closely related to the alveolar injuries in IPF patients.
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影响因子：
5.6
作者：
Leitz DHW;Duerr J;Mulugeta S;Seyhan Agircan A;Zimmermann S;Kawabe H;Dalpke AH;Beers MF;Mall MA
通讯作者：
Mall MA
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：
10.1165/rcmb.2012-0083oc
发表时间：
2013-03-01
影响因子：
6.4
作者：
Gharib, Sina A.;Altemeier, William A.;Chen, Peter
通讯作者：
Chen, Peter
影响因子：
4.3
作者：
Groneberg, DA;Eynott, PR;Chung, KF
通讯作者：
Chung, KF
DOI：
10.1164/rccm.201903-0511oc
发表时间：
2019-12-01
影响因子：
24.7
作者：
Hobbs, Brian D.;Putman, Rachel K.;Viviano, Lisa
通讯作者：
Viviano, Lisa