Morphologically intact airways in lung fibrosis have an abnormal proteome.
Morphologically intact airways in lung fibrosis have an abnormal proteome.
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DOI：
10.1186/s12931-023-02400-x
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发表时间：
2023-04-01
影响因子：
5.8
通讯作者：
中科院分区：
文献类型：
--
作者：
蜂窝样变是一种与肺间质性肺炎（UIP）一致的组织学类型。蜂窝状是指位于致密纤维化部位的囊性气道，具有明显的粘液积聚。利用激光捕获显微切割耦合质谱（LCM-MS），我们询问了10例UIP患者标本中的纤维化蜂窝气道细胞和纤维化未受累气道细胞（远离蜂窝气道且形态完整）。6例患者的非纤维化气道细胞标本作为对照。此外，我们对6例UIP患者和6例粘液腺癌患者中发现的粘液栓进行了LCM-MS。对质谱数据进行定性和定量分析，并通过免疫组织化学进行验证。令人惊讶的是，纤维化未受累气道细胞与蜂窝状气道细胞具有相似的蛋白质谱，显示狭缝和迂回受体（Slit和Robo）途径的失调是最强的类别。我们发现，在UIP中，含有（BPI）折叠的家族B成员1（BPIFB 1）是最显著增加的分泌组相关蛋白，而粘蛋白-5AC（MUC5AC）在粘液腺癌中是最显著增加的。我们的结论是，纤维化未受累气道细胞与纤维化蜂窝状气道细胞有共同的病理特征。此外，纤维化蜂窝气道细胞富含粘蛋白生物发生蛋白，纤毛发生所必需的蛋白质明显紊乱。这种无偏见的空间蛋白质组学方法产生了新的和可检验的假设，以破译纤维化的进展。在线版本包含补充材料，可通过10.1186/s12931 - 023 - 02400-x获得。
Honeycombing is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). Honeycombing refers to cystic airways located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the fibrotic honeycomb airway cells and fibrotic uninvolved airway cells (distant from honeycomb airways and morphologically intact) in specimens from 10 patients with UIP. Non-fibrotic airway cell specimens from 6 patients served as controls. Furthermore, we performed LCM-MS on the mucus plugs found in 6 patients with UIP and 6 patients with mucinous adenocarcinoma. The mass spectrometry data were subject to both qualitative and quantitative analysis and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved airway cells share a similar protein profile to honeycomb airway cells, showing deregulation of the slit and roundabout receptor (Slit and Robo) pathway as the strongest category. We find that (BPI) fold-containing family B member 1 (BPIFB1) is the most significantly increased secretome-associated protein in UIP, whereas Mucin-5AC (MUC5AC) is the most significantly increased in mucinous adenocarcinoma. We conclude that fibrotic uninvolved airway cells share pathological features with fibrotic honeycomb airway cells. In addition, fibrotic honeycomb airway cells are enriched in mucin biogenesis proteins with a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach generates novel and testable hypotheses to decipher fibrosis progression. The online version contains supplementary material available at 10.1186/s12931-023-02400-x.
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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/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5
作者：
Chilosi, M;Poletti, V;Doglioni, C
通讯作者：
Doglioni, C
影响因子：
1.2
作者：
Anselmo, MA;Dalvin, S;Kinane, TB
通讯作者：
Kinane, TB