FIGURE 1.

Schematic diagram illustrating the mechanisms by which several chloride channels affect gene expression in renal fibrosis. (1) CFTR deficiency causes increased intracellular pH. It promotes the binding of positively charged DEP and negatively charged phospholipids at the plasma membrane, and as a result, increased association of FZD and Dvl inhibits the phosphorylated degradation of β-catenin and promotes Wnt/β-catenin signaling. In addition, YAP may play a role in promoting renal fibrosis as one of the mechanisms. (2) TMEM16A stimulated by chloride channel accessory 1 (CLCA1) activates mTORC1-mediated matrix protein synthesis, and GSK-1 induces pro-fibrotic expression in response to TMEM16A-induced activation by increased Cl-concentration. (3)ClC-5 overexpression inhibits NF-κB/MMP-9. FZD: Frizzled; DVL: Dishevelled; AJ: Adherens junctions; ClC-5: voltage-gated chloride channel-5.