Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia.
Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia.
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Na+/H+交换器是脊椎动物粘膜上皮的开发和功能所必需的。
DOI：
10.1159/000492973
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Walentek P
中科院分区：
文献类型：
--
作者：
Sun DI;Tasca A;Haas M;Baltazar G;Harland RM;Finkbeiner WE;Walentek P
Na+/H+交换器 (NHE) 代表高度保守的离子转运蛋白家族，可调节 pH 稳态。 NHE 以及其他质子转运蛋白先前被认为与 Wnt 信号通路、细胞极性信号传导和粘膜纤毛功能的调节有关。此外，基因 SLC9A3（编码 NHE3）的突变被检测为囊性纤维化患者气道感染的额外危险因素。在这里，我们使用非洲爪蟾胚胎粘液纤毛表皮以及人气道上皮细胞（HAEC）作为模型来研究 NHE 在粘液纤毛发育和再生中的功能作用。在非洲爪蟾胚胎中，NHE 1-3 在表皮发育过程中表达，NHE 功能的丧失会损害蝌蚪的粘液纤毛清除能力。清除缺陷是由于纤毛形成减少、多纤毛细胞基体排列紊乱以及粘液纤毛基因表达失调引起的。这些数据还表明 NHE 可能有助于激活粘膜纤毛上皮细胞中的 Wnt 信号传导。在 HAEC 中，NHE 功能的药物抑制也会导致气道多纤毛细胞纤毛和再生缺陷。总的来说，我们的数据揭示了脊椎动物粘液纤毛上皮细胞对 NHE 的需求，并将 NHE 活性与纤毛形成和分化多纤毛细胞的功能联系起来。我们的研究结果为理解 NHE 对人类呼吸道信号传导、发育和发病机制的贡献提供了一个切入点。
Na+/H+exchangers (NHEs) represent a highly conserved family of ion transporters that regulate pH homeostasis. NHEs as well as other proton transporters were previously linked to regulation of the Wnt signaling pathway, cell polarity signaling and mucociliary function. Furthermore, mutations in the gene SLC9A3 (encoding NHE3) were detected as additional risk factors for airway infections in cystic fibrosis patients. Here, we used the Xenopus embryonic mucociliary epidermis as well as human airway epithelial cells (HAECs) as models to investigate the functional roles of NHEs in mucociliary development and regeneration. In Xenopus embryos, NHEs 1-3 were expressed during epidermal development, and loss of NHE function impaired mucociliary clearance in tadpoles. Clearance defects were caused by reduced cilia formation and disrupted alignment of basal bodies in multiciliated cells as well as dysregulated mucociliary gene expression. These data also suggested that NHEs may contribute to the activation of Wnt signaling in mucociliary epithelia. In HAECs, pharmacological inhibition of NHE function also caused defective ciliation and regeneration in airway multiciliated cells. Collectively, our data revealed a requirement for NHEs in vertebrate mucociliary epithelia and linked NHE activity to cilia formation and function in differentiating multiciliated cells. Our results provide an entry point for the understanding of NHE contribution to signaling, development, and pathogenesis of the human respiratory tract.
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影响因子：
16.6
作者：
Corvol H;Blackman SM;Boëlle PY;Gallins PJ;Pace RG;Stonebraker JR;Accurso FJ;Clement A;Collaco JM;Dang H;Dang AT;Franca A;Gong J;Guillot L;Keenan K;Li W;Lin F;Patrone MV;Raraigh KS;Sun L;Zhou YH;O'Neal WK;Sontag MK;Levy H;Durie PR;Rommens JM;Drumm ML;Wright FA;Strug LJ;Cutting GR;Knowles MR
通讯作者：
Knowles MR
影响因子：
10.5
作者：
Ma L;Quigley I;Omran H;Kintner C
通讯作者：
Kintner C
DOI：
10.1083/jcb.200806019
发表时间：
2009-04-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Schneider L;Stock CM;Dieterich P;Jensen BH;Pedersen LB;Satir P;Schwab A;Christensen ST;Pedersen SF
通讯作者：
Pedersen SF
影响因子：
11.8
作者：
Antoniades, Ioanna;Stylianou, Panayiota;Skourides, Paris A.
通讯作者：
Skourides, Paris A.
影响因子：
8
作者：
Oezkucur, Nurdan;Song, Bing;Bola, Sharanya;Zhang, Lei;Reid, Brian;Fu, Guo;Funk, Richard H. W.;Zhao, Min
通讯作者：
Zhao, Min