A Mathematical Model of ENaC and Slc26a6 Regulation by CFTR in Salivary Gland Ducts

Am J Physiol Gastrointest Liver Physiol. 2024 Feb 13. doi: 10.1152/ajpgi.00168.2023. Online ahead of print.ABSTRACTCystic Fibrosis (CF) is a genetic disease caused by the mutations of CFTR, the cystic fibrosis transmembrane conductance regulator gene. Cftr is a critical ion channel expressed in the apical membrane of mouse salivary gland striated duct cells. Although Cftr is primarily a Cl- channel, its knockout leads to higher salivary Cl- and Na+concentrations and lower pH. Mouse experiments show that the activation of Cftr up-regulates ENaC (Epithelial Na+Channel) protein expression level and Slc26a6 (a 1Cl- : 2HCO3- exchanger of the solute carrier family) activity. Experimentally, it is diļ¬€icult to predict how much the co-regulation effects of CFTR contribute to the abnormal Na+ , Cl- and HCO3- concentrations and pH in CF saliva. To address this question we construct a wild-type mouse salivary gland model, and simulate CFTR knockout by altering the expression levels of CFTR, ENaC and Slc26a6. By reproducing the in-vivo and ex-vivo final saliva measurements from wild-type and CFTR knockout animals, we obtain computational evidence that ENaC and Slc26a6 activities are down-regulated in CFTR knockout in salivary glands.PMID:38349781 | DOI:10.1152/ajpgi.00168.2023
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research