Copyright ©The Author(s) 2019.
World J Gastroenterol. Jan 21, 2019; 25(3): 287-299
Published online Jan 21, 2019. doi: 10.3748/wjg.v25.i3.287
Figure 1
Figure 1 Structural features of NCX1.
Figure 2
Figure 2 The regulated signal pathways and transcription factors of NCX1 in digestive diseases. Transforming growth factor-β (TGF-β) stimulates the activation of PLC-IP3 and Ca2+ release from the endoplasmic reticulum, which activates TRPC1 and the reverse mode of NCX1 resulting in Ca2+ influx, and the increase of Ca2+ mediates cell motility directly or indirectly via activation of Ca2+-dependent PKC in pancreatic cancer. Cerulein activates NCX1 and induces activation of inflammatory factors TNF-α and IL-6 and the downstream NK-κB pathway in pancreatic cells. TGF-β can upregulate the expression of NCX1 and TRPC6 and activate the downstream SMAD pathway to regulate the migration and invasion of hepatocellular carcinoma cells.
Figure 3
Figure 3 The effects of NCX1 positive mode in the digestive system. Under normal circumstances, NCX1 adopts the positive mode in esophageal smooth muscle and gastric smooth muscle, excreting Ca2+ from the cells, reducing intracalcium concentration and inducing smooth muscle relaxation. In the jejunum, vitamin D and 1,25-(OH)2D3 can enhance the expression and activity of NCX1 to increase the excretion of Ca2+. NCX1 mainly adopts the forward control mode in ischemic-reperfusion injury. Trisulfated disaccharide (TD) can transport excess intracellular Ca2+ out of the cell by activating NCX1.
Figure 4
Figure 4 The roles of NCX1 reverse mode in the digestive system. In duodenal epithelial cells, carbachol and 5-HT can activate the reverse mode of NCX1, enhancing Ca2+ influx to release HCO3-. In hepatoma cells, NHE1 can promote H+ excretion and Na+ influx and activate the reverse mode of NCX1 to induce Ca2+ influx. In colon goblet cells, ATP activates the TRPM5 channel to induce Na+ influx, and an increase of Na+ concentration starts the NCX1 reverse mode and increases Ca2+ influx and MUC5AC expression. In pancreatic islet β cells, under glucose stimulation, NCX1 can be converted to a reverse mode to promote Ca2+ influx to increase insulin secretion.