Impaired FGF10 Signaling and Epithelial Development in Experimental Lung Hypoplasia With Esophageal Atresia.
Impaired FGF10 Signaling and Epithelial Development in Experimental Lung Hypoplasia With Esophageal Atresia.
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食管闭锁实验性肺发育不全中 FGF10 信号传导和上皮发育受损
DOI：
10.3389/fped.2018.00109
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发表时间：
2018
影响因子：
2.6
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Wang J;Liu H;Gao L;Liu X
食管闭锁（EA）和气管食管瘘（TEF）患者常伴有持续性呼吸道疾病。在实验模型中，阿霉素诱导的发育性肺异常可能是由于分支形态发生因子成纤维细胞生长因子（Fgf10）下调所致。本研究采用定量聚合酶链反应、免疫组织化学和免疫印迹法研究Fgf10通路组分和肺上皮因子在阿霉素诱导的EA-TEF模型中的时空表达。还研究了组蛋白去乙酰化对基因表达的表观遗传调控。在EA-TEF模型中，Fgf10的下游靶点骨形态发生蛋白（Bmp） 4和组织蛋白酶H （Ctsh）在囊状期显著下调，与Fgf10的表达一致。P2x7受体（ati细胞标志物）、Sftpa、Sftpb在肺上皮细胞中的发育表达模式不受影响。Sftpc （atii细胞标志物）和Scgb1a1 （Clara细胞标志物）在小管期显著下调。同时，组蛋白去乙酰化酶（Hdac） 1在EA-TEF模型中上调，随后降低组蛋白H3 Lys56的乙酰化水平，在囊化期恢复到正常水平。综上所述，涉及Fgf10/Ctsh的分子信号干扰与肺形态发生中气道分支和上皮细胞发育受损有关，Sftpc和Scgb1a1蛋白表达下调。Hdac1活性对肺上皮细胞基因和蛋白表达的影响值得进一步研究。
Patients with esophageal atresia (EA) and tracheoesophageal fistula (TEF) often experience persistent respiratory tract disease. In experimental models, doxorubicin-induced developmental lung abnormalities may result from downregulation of branching morphogenesis factor fibroblast growth factor (Fgf10). This study investigated the temporospatial expression of Fgf10 pathway components and lung epithelial factors in an doxorubicin-induced EA-TEF model by quantitative polymerase chain reaction, immunohistochemistry, and immunoblotting. Epigenetic regulation of gene expression by histone deacetylation was also investigated. Bone morphogenetic protein (Bmp) 4 and Cathepsin H (Ctsh), downstream targets of Fgf10, were significantly downregulated in the EA-TEF model during the saccular stage, consistent with Fgf10 expression. The developmental expression pattern of P2x7 receptor (ATI-cell marker), Sftpa, and Sftpb in lung epithelial cells was not affected. Sftpc (ATII-cell Marker) and Scgb1a1 (Clara cell marker) were significantly downregulated at the canalicular stage. Meanwhile, histone deacetylase (Hdac) 1 was upregulated and subsequently decreased acetylation of histone H3 Lys56 in the EA-TEF model, which returned to a normal level at the saccular stage. In conclusion, disturbed molecular signaling involving Fgf10/Ctsh was associated with impaired airway branching and epithelial cell development in lung morphogenesis, as evidenced by downregulated Sftpc and Scgb1a1 protein expression. The influence of Hdac1 activity on gene and protein expression in lung epithelial cells deserves further study.
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组蛋白脱乙酰基酶2介导的糖皮质激素受体的脱乙酰基化可以抑制NF-kappab。
影响因子：
15.3
作者：
Ito, Kazuhiro;Yamamura, Satoshi;Essilfie-Quaye, Sarah;Cosio, Borja;Ito, Misako;Barnes, Peter J;Adcock, Ian M
通讯作者：
Adcock, Ian M
DOI：
10.1002/ar.20799
发表时间：
2009-01
影响因子：
2
作者：
Kim, Namjin;Yamamoto, Hiroaki;Pauling, Michelle Haynes;Lorizio, Walter;Vu, Thiennu H.
通讯作者：
Vu, Thiennu H.
DOI：
10.1165/ajrcmb.20.1.3251
发表时间：
1999-01-01
影响因子：
6.4
作者：
Acarregui, MJ;Penisten, ST;Snyder, JM
通讯作者：
Snyder, JM
影响因子：
1.8
作者：
Lilja, Helene Engstrand;Wester, Tomas
通讯作者：
Wester, Tomas
克拉拉细胞：支气管上皮的祖细胞。
DOI：
10.1016/j.biocel.2009.09.002
发表时间：
2010-01
影响因子：
4
作者：
Reynolds, Susan D.;Malkinson, Alvin M.
通讯作者：
Malkinson, Alvin M.