Insulin Like Growth Factor‐1α Stimulates Differentiation of ATII Cells to ATI‐Like Cells Through Wnt5a

Abstract

Alveolar type II (ATII) epithelial cells are important in the repair of the lung following acute lung injury. ATII cells have the capability to proliferate and differentiate into alveolar type I (ATI) cells in vivo, and can differentiate into an ATI‐like phenotype in vitro. The mechanisms responsible for transdifferentiation are not well understood. In this study we investigated the mechanisms by which insulin‐like growth factor 1‐α (IGF‐1α), which is increased in bronchoalveolar lavage fluid in patients with acute respiratory distress syndrome, promotes rat ATII to ATI differentiation in primary cultures. Gene expression of IGF‐1α was significantly increased in ATI‐like cells compared with ATII cells. Treatment of ATII cells with recombinant IGF‐1α accelerated the transition of ATII to ATI‐like cells, and this effect was inhibited by the IGF‐1α receptor blocker P40. Knockdown of Wnt5a using siRNA slowed the differentiation, as indicated by changes in the expression of ATII and ATI markers. These results suggest that IGF‐1α promotes differentiation of ATII to ATI cells through the non‐canonical Wnt pathway.