The electroneutral Na < sup > + < /sup > -HCO < sub > 3 < /sub > < sup > - < /sup > cotransporter NBCn1 (SLC4A7) modulates colonic enterocyte pH < sub > i < /sub > , proliferation and migration

Am J Physiol Cell Physiol. 2024 Apr 22. doi: 10.1152/ajpcell.00079.2024. Online ahead of print.ABSTRACTNBCn1 (SLC4A7) is one of the two major Na+-HCO3- cotransporters in the human colonic epithelium, expressed predominantly in the highly proliferating colonocytes at the cryptal base. Increased NBCn1 expression levels are reported in tumours, including colorectal cancer. The study explores its importance for maintenance of the intracellular pH (pHi),as well as the proliferative, adhesive, and migratory behavior of the self-differentiating Caco2bbe colonic tumour cell line. In the self-differentiating Caco2BBe cells, NBCn1 mRNA was highly expressed from the proliferative stage until full differentiation. The downregulation of NBCn1 expression by RNA interference affected proliferation and differentiation, and decreased intracellular pH (pHi)of the cells in correlation with the degree of knockdown. In addition, a disturbed cell adhesion and reduced migratory speed were associated with NBCn1 knockdown. Murine colonic Nbcn1-/- enteroids also displayed reduced proliferative activity. In the migrating Caco2BBe cells, NBCn1 was found at the leading edge and in colocalization with the focal adhesion markers vinculin and paxillin, which suggests that NBCn1 is involved in the establishment of cell-matrix adhesion. Our data highlight the physiological significance of NBCn1 in modulating epithelial pH-homeostasis and cell-matrix interactions in the proliferative region of the colonic epit...
Source: American Journal of Physiology. Cell Physiology - Category: Cytology Authors: Source Type: research