Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling.
Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling.
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DOI：
10.1007/s12015-016-9707-z
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发表时间：
2017-04
影响因子：
4.8
通讯作者：
Walters MS
中科院分区：
文献类型：
--
作者：
Gomi K;Tang Y;Arbelaez V;Crystal RG;Walters MS
人气道基底细胞（BC）是人气道上皮的干细胞/祖细胞，能够在更新和修复过程中分化为纤毛细胞和分泌细胞。BC沿基底膜的定位允许间质中非上皮细胞的潜在旁分泌信号来调节BC的功能。鉴于气道上皮和间充质之间的相互作用对两种组织的正常维持至关重要，并且内皮细胞（EC）可以调节BC的多种功能，本研究旨在帮助理解BC和EC串扰在调节BC干/祖细胞功能中的作用。使用体外共培养系统模拟这些细胞类型的体内物理分离，我们评估了原发性肺微血管EC对原发性BC分化为粘液纤毛上皮的影响。数据表明，BC和肺微血管EC的共培养通过激活BC中胰岛素（INS）和胰岛素样生长因子1 （IGF1）受体（INSR和IGF1R）介导的信号传导，导致BC纤毛细胞分化增加。与此数据一致，siRNA介导的BC中INSR和IGF1R的下调抑制了纤毛细胞的分化。总之，这些发现确定了BC向纤毛细胞分化所需的重要信号通路，并证明了BC- ec串扰在调节正常气道上皮结构中的重要性。
Human airway basal cells (BC) function as stem/progenitor cells of the human airway epithelium, capable of differentiating into ciliated and secretory cells during turnover and repair. The positioning of BC along the basement membrane allows for potential paracrine signaling from non-epithelial cells in the mesenchyme to regulate BC function. Based on the knowledge that interaction between the airway epithelium and mesenchyme is critical for proper maintenance of both tissues, and that endothelial cells (EC) can regulate multiple functions of BC, the present study was designed to help understand the role of BC and EC cross-talk in regulating BC stem/progenitor function. Using an in vitro co-culture system that mimics the in vivo physical separation of these cell types, we assessed the impact of primary lung microvascular EC on differentiation of primary BC into a mucociliated epithelium. The data demonstrate that co-culture of BC and lung microvasculature EC results in increased ciliated cell differentiation of BC via activation of insulin (INS) and insulin-like growth factor 1 (IGF1) receptor (INSR and IGF1R) mediated signaling in BC. Consistent with this data, siRNA mediated knockdown of INSR and IGF1R in BC suppressed ciliated cell differentiation. Together these findings identify an important signaling pathway required for differentiation of BC into a ciliated cells and demonstrate the importance of BC-EC cross-talk in regulating normal airway epithelial structure.
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影响因子：
5.2
作者：
Malaguarnera R;Belfiore A
通讯作者：
Belfiore A
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
分子途径：胰岛素样生长因子-1受体途径阻滞的临床应用和未来方向。
DOI：
10.1158/1078-0432.ccr-14-2518
发表时间：
2015-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Iams WT;Lovly CM
通讯作者：
Lovly CM
影响因子：
8
作者：
Curradi, Giacomo;Walters, Matthew S.;Ding, Bi-Sen;Rafii, Shahin;Hackett, Neil R.;Crystal, Ronald G.
通讯作者：
Crystal, Ronald G.
影响因子：
4.9
作者：
Fidler, Mary Jo;Shersher, David D.;Bonomi, Philip
通讯作者：
Bonomi, Philip