Folliculin controls lung alveolar enlargement and epithelial cell survival through E-cadherin, LKB1, and AMPK.
Folliculin controls lung alveolar enlargement and epithelial cell survival through E-cadherin, LKB1, and AMPK.
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DOI：
10.1016/j.celrep.2014.03.025
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发表时间：
2014-04-24
期刊：
影响因子：
8.8
通讯作者：
Krymskaya VP
中科院分区：
文献类型：
--
作者：
Goncharova EA;Goncharov DA;James ML;Atochina-Vasserman EN;Stepanova V;Hong SB;Li H;Gonzales L;Baba M;Linehan WM;Gow AJ;Margulies S;Guttentag S;Schmidt LS;Krymskaya VP
Spontaneous pneumothoraces due to lung cyst rupture afflict patients with the rare disease Birt-Hogg-Dubé (BHD) syndrome caused by mutations of the tumor suppressor gene folliculin (FLCN) by unknown mechanism. BHD lungs exhibit increased alveolar epithelial cell apoptosis. We show that Flcn deletion in lung epithelium leads to cell apoptosis, alveolar enlargement and impaired lung function. FLCN loss also impairs alveolar epithelial barrier function. Flcn-null epithelial cell apoptosis is the result of impaired AMPK activation and increased cleaved caspase-3. AMPK activator LKB1 and E-cadherin are downregulated by Flcn loss and restored by its expression. Flcn-null cell survival is rescued by AICAR or constitutively active AMPK. AICAR also improves lung condition of Flcnf/f:SP-C-Cre mice. Our data show that Flcn regulates lung epithelial cell survival and alveolar size and suggest that lung cysts in BHD may result from an underlying defect in alveolar epithelial cell survival attributable to FLCN regulation of the E-cadherin-LKB1-AMPK axis.
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影响因子：
4.8
作者：
Liu, Chao;Liang, Bin;Zou, Ming-Hui
通讯作者：
Zou, Ming-Hui
DOI：
10.1165/rcmb.2008-0137oc
发表时间：
2009-10-01
影响因子：
6.4
作者：
Mouded, Majd;Egea, Eduardo E.;Shapiro, Steven D.
通讯作者：
Shapiro, Steven D.
影响因子：
37.3
作者：
Hong SB;Oh H;Valera VA;Stull J;Ngo DT;Baba M;Merino MJ;Linehan WM;Schmidt LS
通讯作者：
Schmidt LS
影响因子：
2.2
作者：
Gupta, Nishant;Seyama, Kuniaki;McCormack, Francis X.
通讯作者：
McCormack, Francis X.
影响因子：
5.3
作者：
Goncharova, Elena A.;Goncharov, Dmitry A.;Krymskaya, Vera P.
通讯作者：
Krymskaya, Vera P.