Molecular mechanisms involved in TNF - and gastrin-mediated gene regulation

Abstract

Cells in a multicellular organism depend on extensive communication with each other. Eukaryotic cells have developed elaborate signal transduction systems by which externally provided information (hormones, cytokines, growth factors, ions and other signaling molecules) is converted into intracellular information that regulates the internal workings of the cell, such as transcription of genes. This can be exemplified by gastric acid production in humans. Secretion of gastric acid is regulated by the peptide hormone gastrin, and involves an interplay between different cells in the stomach mucosa as well as induction of gene expression (Figure 1). The physiological response to food intake includes release of gastrin from G-cells. Gastrin binds to receptors on the ECL-cells and thereby induces histamine release from internal vesicles. Histamine in turn acts upon parietal cells that are stimulated to produce and secrete gastric acid. The regulatory functions of gastrin also include release of somatostatin from D-cells and induction of histidine decarboxylase (HDC) gene expression. HDC catalyses the ratelimiting step in histamine production in ECL-cells.