Ontogeny of CLCN3 chloride channel gene expression in human pulmonary epithelium

Human fetal bronchopulmonary epithelia secrete liquid, and this chloride (C I)-dependent process is important for normal lung growth. At the time of bi rth there is a maturational transition from a secretory to an absorptive ph enotype. The pathways for CI exit from the epical membrane which are requir ed for fetal lung liquid secretion are unknown but are thought to be indepe ndent of the cystic fibrosis transmembrane conductance regulator. We determ ined the ontogeny of expression of the CLCN family of voltage-dependent CI channel genes (CLCN2 through 6, K-a and K-b) in the human lung to identify potential pathways for pulmonary liquid secretion. Only CLCN3 and CLCN6 mes senger RNA were detected by Northern analysis of fetal whole lung tissue. R ibonuclease protection assays confirmed the expression of CLCN3 and also re vealed expression of CLCN2, The ontogeny of expression of these two channel s was similar, peaking in midgestation and declining postnatally. In situ h ybridization localized the CLCN2 and CLCN3 messages to airway and distal pu lmonary epithelia and to pulmonary blood vessels. We conclude that CLCN3 is expressed in human airway epithelia and expression is developmentally regu lated. The contribution of these channels to pulmonary epithelial liquid tr ansport and lung development remains to be determined.