Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells.
Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells.
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DOI：
10.1007/s00018-012-0922-8
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发表时间：
2012-07
影响因子：
8
通讯作者：
Crystal, Ronald G.
中科院分区：
文献类型：
--
作者：
Curradi, Giacomo;Walters, Matthew S.;Ding, Bi-Sen;Rafii, Shahin;Hackett, Neil R.;Crystal, Ronald G.
人气道上皮是由纤毛细胞、分泌细胞、中间细胞和基底细胞组成的假复层异质层。作为气道上皮的干/祖细胞群，气道基底细胞分化为纤毛细胞和分泌细胞以在生理更新和修复期间补充气道上皮。气道基底细胞的转录组分析显示血管内皮生长因子A（VEGFA）的高表达，该基因通常与这种细胞类型的功能无关。使用原代人气道基底细胞的培养物，我们证明基底细胞表达VEGFA的所有3种主要亚型（121、165和189），但缺乏经典VEGFA受体VEGFR 1和VEGFR 2的功能性表达。VEGFA由基底细胞主动分泌，虽然它似乎对基底细胞生长和增殖没有直接的自分泌功能，但它以旁分泌方式起作用，通过VEGFR 2依赖性信号传导途径激活内皮中的MAPK信号传导级联。使用原代人气道基底细胞和人内皮细胞的无细胞因子和无血清共培养系统揭示了基底细胞分泌的VEGFA激活内皮细胞以表达介质，所述介质继而刺激和支持基底细胞增殖和生长。这些数据证明了新的VEGFA介导的气道基底细胞和内皮之间的串扰，其目的是调节内皮活化，进而刺激和维持基底细胞生长。
The human airway epithelium is a pseudostratified heterogenous layer comprised of ciliated, secretory, intermediate and basal cells. As the stem/progenitor population of the airway epithelium, airway basal cells differentiate into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. Transcriptome analysis of airway basal cells revealed high expression of vascular endothelial growth factor A (VEGFA), a gene not typically associated with the function of this cell type. Using cultures of primary human airway basal cells, we demonstrate that basal cells express all of the 3 major isoforms of VEGFA (121, 165 and 189) but lack functional expression of the classical VEGFA receptors VEGFR1 and VEGFR2. The VEGFA is actively secreted by basal cells and while it appears to have no direct autocrine function on basal cell growth and proliferation, it functions in a paracrine manner to activate MAPK signaling cascades in endothelium via VEGFR2 dependent signaling pathways. Using a cytokine- and serum-free co-culture system of primary human airway basal cells and human endothelial cells revealed that basal cell secreted VEGFA activated endothelium to express mediators that, in turn, stimulate and support basal cell proliferation and growth. These data demonstrate novel VEGFA mediated cross-talk between airway basal cells and endothelium, the purpose of which is to modulate endothelial activation and in turn stimulate and sustain basal cell growth.
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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
影响因子：
3.7
作者：
Hackett NR;Shaykhiev R;Walters MS;Wang R;Zwick RK;Ferris B;Witover B;Salit J;Crystal RG
通讯作者：
Crystal RG
影响因子：
158.5
作者：
AUERBACH, O;GERE, JB;STOUT, AP
通讯作者：
STOUT, AP
影响因子：
5.8
作者：
Franzdóttir SR;Axelsson IT;Arason AJ;Baldursson O;Gudjonsson T;Magnusson MK
通讯作者：
Magnusson MK
影响因子：
2.6
作者：
Alagappan, Vijay K. T.;Willems-Widyastuti, Anna;Sharma, Hari S.
通讯作者：
Sharma, Hari S.