[Tissue-specific expression of Na+ -H+ exchanger isoforms at two developmental stages of human fetus]

Na(+)-H(+) exchangers (NHE) are major membrane proteins that have been identified as signal transduction mediators in the regulation of cell differentiation and important membrane ion transporters in the regulation of the intercellular pH and the cell volume. NHE are composed of at least six isoforms and activated in growth factor-regulated cell differentiation. However, little is known about the differential regulation of NHE expression in the development. In the present study, we studied developmental regulation of the expression of NHE isoforms in human fetal tissues by comparing the expression of various isoforms between two developmental stages, i.e., week 11 (11 W) and week 16 (16 W). The results demonstrated that NHE1 transcripts were expressed ubiquitously. In comparison to the expression at 16 W, the level of NHE1 transcripts was low and varied significantly in a tissue-specific pattern at 11 W, suggesting that the house-keeping function of MHE1 occurs at 11 W or earlier and becomes well established at least as early as at 16 W. The tissue-specifically restricted expression of NHE2 and NHE3 was regulated at 11 W and 16 W in an opposite tendency, supporting the overlapping relationship between NHE2 and NHE3 in the tissue distribution as reported in adults. NHE5 expression was relatively ubiquitous at 11 W and became restricted in the cerebellum at 16 W, suggesting that the restrictive expression of NHE5 in the brain occurs later than that of other isoforms. The present study demonstrates a space time-dependent regulation of the tissue-specific expression pattern of NHE isoforms during human development between 11 W and 16 W. The results also suggest that at 16 W or earlier the expression pattern of developing tissues becomes similar to that of adult tissues. The observed developmental regulation of NHE expression provides a molecular basis for further study of the function and regulation of NHE gene during development.