The role of TGFβ-HGF-Smad4 axis in regulating the proliferation of mouse airway progenitor cells

The interaction between airway epithelial progenitor cells and their microenvironment is critical for maintaining lung homeostasis. This microenvironment includes fibroblast cells, which support the growth of airway progenitor cells. However, the mechanism of this support is not fully understood. In the present study, the authors observed that inhibition of transforming growth factor (TGF)-beta signal with SB431542 promotes the expression of hepatocyte growth factor (HGF) in fibroblast cells. The HGF receptor, c-Met, is expressed on airway progenitor cells; HGF promotes the colony-forming ability of airway progenitor cells. The deletion of Smad4 in airway progenitor cells increases the colony-forming ability, suggesting that Smad4 plays a negative role in the regulating the proliferation of airway progenitor cells. These data demonstrated that the regulation of airway progenitor cells by TGF-beta depends on TGF-beta R1/2 on stromal cells, rather than on epithelial progenitor cells. These data suggested a role for the TGF-beta-TGF-beta R1/2-HGF-Smad4 axis in airway epithelial homeostasis and sheds new light on the interaction between airway progenitor cells and their microenvironment.