Keratinocyte Growth Factor and Autocrine Repair in Airway Epithelium

Abstract

Background: Delayed or nonreepithelialization of the large conducting airway (ie, trachea and bronchus) is a clinically recognized but poorly understood result of airway trauma. This delay results in granulation tissue formation and scarring, which impairs mucocilliary transport and can critically compromise gas exchange. Keratinocyte growth factor (KGF) is a known epithelial cell mitogen that is derived from mesenchymal cells. We previously observed its expression in injured tracheal explants, and in the present study we investigated its origin. Design: Freshly isolated porcine tracheal epithelial cells were cytospun onto glass slides for immunohistochemical identification and localization of KGF and for in situ hybridization localization of its messenger RNA. Polymerase chain reaction analysis for KGF was also performed. Results: Freshly isolated respiratory epithelial cells were identified as being of epithelial origin and uncontaminated by fibroblasts, as evidenced by stains that were positive for AE3 and negative for vimentin. Immunohistochemical analysis and in situ hybridization revealed a subset of cells that were positive for both the protein and the message for KGF. Conclusion: This subset of KGF-expressing respiratory epithelial cells may participate in a hitherto undescribed autocrine loop for stimulating KGF production in response to injury.

Basal cells express functional TRPV4 channels in the mouse nasal epithelium

“…In the AE, basal cells are progenitor cells, and they can repopulate other cell types after injury in mice and humans [4] , [33] . Receptors for keratinocyte growth factor (KGF) [8] and epidermal growth factor (EGF) [9] , [34] , which are involved in the repair of injured epithelia, are co-localized with a population of basal cells in the AE, but little is known about their regulation. In addition, these stem cells may contribute to epithelial immunity by secreting the antimicrobial protein RNase 7 in response to transient epithelial injury [35] .…”

Potential of Heterotopic Fibroblasts as Autologous Transplanted Cells for Tracheal Epithelial Regeneration

“…Normal tracheal epithelial regeneration requires the secretion of appropriate diffusible factors by TFBs, such as keratinocyte growth factor, epidermal growth factor, and hepatocyte growth factor. [35][36][37][38] GFBs have been reported to secrete these diffusible FIG. 5.…”

Effect of Fibroblasts on Tracheal Epithelial Regeneration in vitro

“…39,40 In the trachea, keratinocyte growth factor has been identified that stimulates the proliferation and differentiation of epithelial cells and modulates basal expression of mucin genes, interacting with retinoic acid in a concentration-dependent manner. 41,42 EGF activates epithelial cell migration. 43 Hepatocyte growth factor influences the differentiation of epithelial cells through the activation of c-met at the basolateral surface of these cells.…”