Caveolin‐1 regulation of mouse lung epithelial progenitor cell differentiation and morphogenesis.

Abstract

Caveolin‐1 (Cav‐1) is an intracellular scaffolding protein that regulates cell signaling and caveolae formation. We previously observed morphological and patterning defects in Cav‐1−/− mouse lungs and thus hypothesized that Cav‐1 may play an important role in the regulation of lung epithelial cell differentiation and morphogenesis. Distal lung epithelial progenitor cells (LEPCs) isolated from wild‐type (WT) and Cav‐1−/− mouse lungs expressed generic epithelial markers E‐cadherin and pan‐cytokeratin, but were negative for differentiation markers Clara Cell Secretary Protein (CCSP) and Aquaporin‐5 (AQP5). Cav‐1−/− LEPC colonies grown on plastic showed disrupted E‐cadherin and ß‐catenin junctional staining after induction of differentiation by addition of high calcium. qRT‐PCR and Western blot analysis of WT and Cav‐1−/− cells cultured in matrigel showed induction of CCSP and AQP5 in WT cells only. Also, epithelial cell cyst formation was observed in both WT and Cav‐1−/− cells, however cyst diameter was significantly greater for Cav‐1−/− cysts. From these studies, we speculate that defective differentiation and cell‐cell communication in the absence of Cav‐1 leads to dysfunctional distal lung epithelial cell morphogenesis.