| First Author | Rottgen TS | Year | 2018 |
| Journal | Am J Physiol Cell Physiol | Volume | 315 |
| Issue | 1 | Pages | C10-C20 |
| PubMed ID | 29561662 | Mgi Jnum | J:264688 |
| Mgi Id | MGI:6188371 | Doi | 10.1152/ajpcell.00328.2017 |
| Citation | Rottgen TS, et al. (2018) Dextran sulfate sodium-induced chronic colitis attenuates Ca(2+)-activated Cl(-) secretion in murine colon by downregulating TMEM16A. Am J Physiol Cell Physiol 315(1):C10-C20 |
| abstractText | Attenuated Ca(2+)-activated Cl(-) secretion has previously been observed in the model of dextran sulfate sodium (DSS)-induced colitis. Prior studies have implicated dysfunctional muscarinic signaling from basolateral membranes as the potential perpetrator leading to decreased Ca(2+)-activated Cl(-) secretion. However, in our chronic model of DSS-colitis, cholinergic receptor muscarinic 3 ( Chrm3) transcript (1.028 +/- 0.12 vs. 1.029 +/- 0.27, P > 0.05) and CHRM3 protein expression (1.021 +/- 0.24 vs. 0.928 +/- 0.09, P > 0.05) were unchanged. Therefore, we hypothesized that decreased carbachol (CCH)-stimulated Cl(-) secretion in DSS-induced colitis could be attributed to a loss of Ca(2+)-activated Cl(-) channels (CaCC) in apical membranes of colonic epithelium. To establish this chemically-induced colitis, Balb/C mice were exposed to 4% DSS for five alternating weeks to stimulate a more moderate, chronic colitis. Upon completion of the protocol, whole thickness sections of colon were mounted in an Ussing chamber under voltage-clamp conditions. DSS-induced colitis demonstrated a complete inhibition of basolateral administration of CCH-stimulated Cl(-) secretion that actually displayed a reversal in polarity (15.40 +/- 2.22 muA/cm(2) vs. -2.47 +/- 0.25 muA/cm(2)). Western blotting of potential CaCCs, quantified by densitometric analysis, demonstrated no change in bestrophin-2 and cystic fibrosis transmembrane regulator, whereas anoctamin-1 [ANO1, transmembrane protein 16A (TMEM16A)] was significantly downregulated (1.001 +/- 0.13 vs. 0.510 +/- 0.12, P < 0.05). Our findings indicate that decreased expression of TMEM16A in DSS-induced colitis contributes to the decreased Ca(2+)-activated Cl(-) secretion in murine colon. |
