Expression of C-type Natriuretic Peptide and Natriuretic Peptide Receptors in the Mouse Submandibular Glands Following Embryonic Development, Postnatal Differentiation and Aging / 대한해부학회지

ABSTRACT

C-type natriuretic peptide (CNP), a member of natriuretic peptide family, is mainly synthesized in the endothelium and central nervous system. But CNP is also involved in the growth and differentiation of other peripheral organs. Although we have reported the local synthesis and localization of CNP in the adult submandibular glands (SMG), it is not known that the expression and biological activity of CNP following the morphogenesis, differentiation and aging. This study aimed to examine the expression of CNP and its receptors in the developing and differentiating stages of mouse SMG, and the changes of biological activity of its receptors with aging. The SMG, obtained from 14, 16, 18 days-old embryos (E) and 1 day, 2 weeks, 1, 2, 12, and 24 month-old C57BL/6N mouse, were processed for RT-PCR, in situ hybridization, immunohistochemistry and cGMP assay. CNP was strongly expressed in the epithelial clusters of primitive SMG, which was maintained before birth but was markedly decreased after birth. CNP was localized in the intercalated duct and granular convoluted tubules of adult SMG, where NPRC was specifically expressed but NPRB was not. CNP mRNA was gradually decreased from E16 to 2 M but ANP mRNA was opposed. NPRB and NPRC were the same pattern of the expression of CNP but NPRA was weakly expressed. In addition, CNP mRNA was also expressed in the craniofacial tissues such as tooth germs, tongue, premaxilla and bone forming area in which NPRC was specifically expressed but NPRB was not. In the SMG of 2 M, the membrane of duct cells markedly produced cGMP by CNP whereas acini produced cGMP by ANP and BNP rather than CNP. The biological activity of cGMP production of SMG gradually decreased with age. cGMP production was dominant by CNP in SMG of 1M but was by ANP after 2M. These results shows that CNP may play roles both in the morphogenesis and differentiation via NPRC and in the maintenance of duct system via NPRB in the mouse SMG and that the biological activity of its receptors may decreased with aging.