The Role of pHi in Intestinal Epithelial Proliferation-Transport Mechanisms, Regulatory Pathways, and Consequences

Abstract

During the maturation of intestinal epithelial cells along the crypt/surface axis, a multitude of acid/base transporters are differentially expressed in their apical and basolateral membranes, enabling processes of electrolyte, macromolecule, nutrient, acid/base and fluid secretion, and absorption. An intracellular pH (pH_i)-gradient is generated along the epithelial crypt/surface axis, either as a consequence of the sum of the ion transport activities or as a distinctly regulated entity. While the role of pH_i on proliferation, migration, and tumorigenesis has been explored in cancer cells for some time, emerging evidence suggests an important role of the pH_i in the intestinal stem cells (ISCs) proliferative rate under physiological conditions. The present review highlights the current state of knowledge about the potential regulatory role of pH_i on intestinal proliferation and differentiation.

Keywords: epithelial ion transport; intestinal epithelial cells; intracellular pH; proliferation; signaling pathways.