The renin-angiotensin system promotes colonic inflammation by inducing TH17 activation via the JAK2/STAT pathway.

The renin-angiotensin system promotes colonic inflammation by inducing TH17 activation via the JAK2/STAT pathway. Am J Physiol Gastrointest Liver Physiol. 2019 Apr 17;: Authors: He L, Du J, Chen Y, Liu C, Zhou M, Adhikari S, Rubin DT, Pekow J, Li YC Abstract Previous studies suggest that the renin-angiotensin system (RAS) is pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (Ang II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and Ang II levels were markedly increased in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis. Renin transgenic (RenTg) mice exhibited increased phosphorylation in JAK2 and STAT1/3 within colonic mucosa at baseline and following TNBS induction, suggesting that Ang II promotes colonic inflammation via JAK2/STAT1/3 pathway. Treatment with pan-JAK inhibitor tofacitinib blocked JAK2 and STAT1/3 phosphorylation, attenuated TH1 and TH17 responses, alleviated colitisand prevented death of RenTg mice in TNBS model. Ang II stimulated JAK2/STAT1/3 phosphorylation in both Jurkat T lymphocytes and HCT116 epithelial cells. In vitropolarization assays demonstrated that Ang II directly promoted TH17 polarization, but not TH1 polarization, via JAK2/STAT1/3. Ang II stimul...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research