Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling

Kazunori Gomi, Yongjiang Tang, Vanessa Arbelaez, Ronald Crystal, Matthew S. Walters

Research output: Contribution to journalArticle

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)309-317
Number of pages9
JournalStem Cell Reviews and Reports
Issue number2
Publication statusPublished - 1 Apr 2017
Externally publishedYes



  • Basal stem/progenitor cells
  • Ciliated cells
  • Differentiation
  • Endothelial cells
  • Human airway epithelium
  • Insulin
  • Insulin-like growth factor 1
  • Signaling

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

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