Parabronchial smooth muscle cell (PSMC) progenitors prompt epithelial proliferation by secreting fibroblast growth factor 10 (Fgf10) during lung development. A new study shows that these cells also act as a self-renewal niche after airway epithelium injury, leading to lung repair in adult mice (J. Clin. Invest. doi:10.1172/JCI58097).

Thomas Volckaert and his colleagues found that treatment of mice with naphthalene leads to the injury (or loss) of Clara epithelial cells. In response, Wnt signaling is reactivated in mature PSMCs, which secrete Fgf10 that then activates surviving variant Clara cells in a paracrine manner, allowing these cells to help replace epithelium. Fgf10-mediated activation induces Snail1 expression and Notch activation in the Clara cells, resulting in an epithelial-to-mesenchymal transition that promotes lung epithelium repair and may indicate an epithelial stem cell–like state.

Fgf10 from the PMSC niche may therefore be involved in lung development and airway epithelium regeneration after injury. Further investigation will be required to elucidate the role of Wnt and Fgf10 signaling during abnormal repair and remodeling in people suffering from chronic injury to these tissues, such as in asthma.