The expression profile of Claudin family members in the developing mouse lung and expression alterations resulting from exposure to secondhand smoke (SHS)

Abstract

ABSTRACTClaudins are tight junctional proteins implicated in cell polarity and epithelial barrier maintenance. Claudin misregulation adversely impacts developmental aspects of cell differentiation and proliferation. The current research evaluated transcriptional expression for Claudins 1–11 and 18 in the developing murine lung at embryonic days (E) 14.5, 16.5, and 18.5 and at post-natal day (PN) 3 and PN15. Mouse lungs were also assessed by immunohistochemical analysis to qualitatively evaluate Claudin protein expression. Pregnant dams were further exposed to secondhand smoke (SHS) from embryonic day (E)15.5 to 18.5 and Claudin mRNA was immediately screened in pup lungs. Other than Claudin-6, mRNA expression patterns for Claudin family members tended to decrease at E16.5, increase at E18.5, and decrease again at PN3 before reaching a peak of expression at PN15. Claudin-6 mRNA expression decreased through gestation and into post-natal periods. Immunohistochemical profiling implicated a subset of Claudins as plausible orchestrators of proximal vs. distal lung barrier establishment. Assessment of Claudin mRNA expression at E18.5 following SHS exposure revealed a significant reduction in transcription for all Claudins except Claudin-18 (no change). These data support the need for further studies using gene targeted mice that knock-in/out specific Claudins so that precise functions in the normal and diseased lung can be determined.