Constitutive STAT3 serine phosphorylation promotes Helicobacter-mediated gastric disease.

Constitutive STAT3 serine phosphorylation promotes Helicobacter-mediated gastric disease. Am J Pathol. 2020 Mar 19;: Authors: Balic JJ, Saad MI, Dawson R, West AJ, McLeod L, West AC, D'Costa K, Deswaerte V, Dev A, Sievert W, Gough DJ, Bhathal PS, Ferrero RL, Jenkins BJ Abstract Gastric cancer is associated with chronic inflammation (gastritis) triggered by infection with the Helicobacter pylori (H. pylori) bacterium. Elevated tyrosine phosphorylation (pY) of the latent transcription factor STAT3 is a feature of gastric cancer, including H. pylori-infected tissues, and is aligned to nuclear transcriptional activity. By contrast, the transcriptional role of STAT3 serine phosphorylation (pS), which promotes STAT3-driven mitochondrial activities, is unclear. Here, by coupling pS-STAT3-deficient Stat3SA/SA mice with chronic H. felis infection, we reveal a key role for pS-STAT3 in promoting Helicobacter-induced gastric pathology. Immunohistochemical staining for infiltrating immune cells, and expression analyses of inflammatory genes, revealed that chronic gastritis was markedly suppressed in infected Stat3SA/SA mice compared to wild-type (WT) mice. Stomach weight and gastric mucosal thickness were also reduced in infected Stat3SA/SA (compared to WT) mice, which was associated with reduced proliferative potential of infected Stat3SA/SA gastric mucosa. The suppressed H. felis-induced gastric phenotype of Stat3SA/SA mice was phenocopied upon...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research