Expression Profile of Claudin Family Members in the Developing Lung

Abstract

Claudins are tight junctional proteins that are implicated in cell polarity and in establishing and maintaining epithelial barrier function. Our published research has also revealed that claudin misregulation adversely impacts cell differentiation and proliferation. Impairment of such critical functions related to various claudins has been linked to anomalous barriers in abnormal lung development and diseases such as acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and cancer. The current research evaluated expression of claudins 1‐8 in order to elucidate expression patterns within the developing murine lung. Claudins 1‐8 were selected based on their phylogenetic similarity and published reports of potentially diverse pulmonary expression patterns. Wild type mice from embryonic days 12.5, 14.5, 16.5, 18.5 and post‐natal day 2 were sacrificed and assessed to demonstrate cell‐specific expression via immunohistochemical analysis. Protein and RNA expression was quantitatively confirmed using immunoblotting and qPCR techniques. The results suggest increasing and decreasing patterns of expression that included redundancies and temporal transition between family members. Furthermore, cell‐specific expression of individual claudins implicated a subset as orchestrators of proximal vs. distal lung barrier establishment. These data support the need for further studies using claudin‐specific transgenic mice that knock‐in/out specific claudins so that precise functions in the normal and diseased lung can be determined. This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).