Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice.
Deletion of SMARCA4 impairs alveolar epithelial type II cells proliferation and aggravates pulmonary fibrosis in mice.
复制标题
SMARCA4缺失损害小鼠肺泡II型上皮细胞增殖并加重肺纤维化
DOI：
10.1016/j.gendis.2017.10.001
复制
发表时间：
2017-12
期刊：
影响因子：
6.8
通讯作者：
Fu Z
中科院分区：
文献类型：
--
作者：
Peng D;Si D;Zhang R;Liu J;Gou H;Xia Y;Tian D;Dai J;Yang K;Liu E;Shi Y;Lu QR;Zou L;Fu Z
肺泡上皮细胞（AECs）损伤和AECs屏障重建失败都是肺泡灌洗液和随后的肺纤维化（PF）的组成部分。然而，调控AEC损伤后再生的确切机制仍不清楚。SMARCA 4是大的ATP依赖性染色质重塑复合物SWI/SNF的一部分，其对肾脏和心脏纤维化至关重要。本研究首次建立了博莱霉素诱导的PF小鼠肺纤维化模型，研究SMARCA 4在肺纤维化中的作用，发现SMARCA 4主要在肺泡II型（ATII）细胞中表达增强。此外，我们建立了肺泡上皮特异性SMARCA 4缺失的SP-C-rtTA/（tetO）7-Cre/SMARCA 4f/f小鼠（SOSM 4 Δ/Δ）模型，以及新的SMARCA 4缺失的肺泡II型（ATII）样mle-12细胞系。我们发现博来霉素诱导的PF在SOSM 4 Δ/Δ小鼠中更具攻击性。此外，ATII细胞的增殖随着SMARCA 4在体内和体外的损失而降低。此外，我们观察到ATII细胞的增殖增加，伴随着人PF肺切片中SMARCA 4的异常高表达。这些数据揭示了SMARCA 4在ATII细胞增殖中不可或缺的作用，这可能影响PF的进展。
Alveolar epithelial cells (AECs) injury and failed reconstitution of the AECs barrier are both integral to alveolar flooding and subsequent pulmonary fibrosis (PF). Nevertheless, the exact mechanisms regulating the regeneration of AECs post-injury still remain unclear. SMARCA4 is a part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is essential for kidney and heart fibrosis. We investigates SMARCA4 function in lung fibrosis by establishing PF mice model with bleomycin firstly and found that the expression of SMARCA4 was mainly enhanced in alveolar type II (ATII) cells. Moreover, we established an alveolar epithelium-specific SMARCA4-deleted SP-C-rtTA/(tetO)7-Cre/SMARCA4f/f mice (SOSM4Δ/Δ) model, as well as a new SMARCA4-deleted alveolar type II (ATII)-like mle-12 cell line. We found that the bleomycin-induced PF was more aggressive in SOSM4Δ/Δ mice. Also, the proliferation of ATII cells was decreased with the loss of SMARCA4 in vivo and in vitro. In addition, we observed increased proliferation of ATII cells accompanied by abnormally high expression of SMARCA4 in human PF lung sections. These data uncovered the indispensable role of SMARCA4 in the proliferation of ATII cells, which might affect the progression of PF.
登录
查看更多内容
DOI：
10.1073/pnas.1107559108
发表时间：
2011-06-28
影响因子：
11.1
作者：
Lawson, William E.;Cheng, Dong-Sheng;Blackwell, Timothy S.
通讯作者：
Blackwell, Timothy S.
影响因子：
15.9
作者：
Chapman, Harold A.;Li, Xiaopeng;Vu, Thiennu H.
通讯作者：
Vu, Thiennu H.
DOI：
10.1164/rccm.2009-040gl
发表时间：
2011-03-15
影响因子：
24.7
作者：
Raghu, Ganesh;Collard, Harold R.;Schuenemann, Holger J.
通讯作者：
Schuenemann, Holger J.
影响因子：
11.2
作者：
Orvis T;Hepperla A;Walter V;Song S;Simon J;Parker J;Wilkerson MD;Desai N;Major MB;Hayes DN;Davis IJ;Weissman B
通讯作者：
Weissman B
影响因子：
10
作者：
DePianto DJ;Chandriani S;Abbas AR;Jia G;N'Diaye EN;Caplazi P;Kauder SE;Biswas S;Karnik SK;Ha C;Modrusan Z;Matthay MA;Kukreja J;Collard HR;Egen JG;Wolters PJ;Arron JR
通讯作者：
Arron JR