The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Up-regulation of NHE8 by somatostatin ameliorates the diarrhea symptom in infectious colitis mice model

  • Lei, Xuelian (Department of Gastroenterology, West China Hospital of Sichuan University) ;
  • Cai, Lin (Department of Gastroenterology, West China Hospital of Sichuan University) ;
  • Li, Xiao (Department of Gastroenterology, West China Hospital of Sichuan University) ;
  • Xu, Hua (University of Arizona Health Science Center) ;
  • Geng, Chong (Department of Gastroenterology, West China Hospital of Sichuan University) ;
  • Wang, Chunhui (Department of Gastroenterology, West China Hospital of Sichuan University)
  • Received : 2017.07.28
  • Accepted : 2017.12.14
  • Published : 2018.05.01
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Abstract

$Na^+/H^+$ exchangers (NHEs) have been shown to be involved in regulating cell volume and maintaining fluid and electrolyte homeostasis. Pooled evidences have suggested that loss of $Na^+/H^+$ exchanger isoform 8 (NHE8) impairs intestinal mucosa. Whether NHE8 participates in the pathology of infectious colitis is still unknown. Our previous study demonstrated that somatostatin (SST) could stimulate the expression of intestinal NHE8 so as to facilitate $Na^+$ absorption under normal condition. This study further explored whether NHE8 participates in the pathological processes of infectious colitis and the effects of SST on intestinal NHE8 expression in the setting of infectious colitis. Our data showed that NHE8 expression was reduced in Citrobacter rodentium (CR) infected mice. Up-regulation of NHE8 improved diarrhea symptom and mucosal damage induced by CR. In vitro, a similar observation was also seen in Enteropathogenic E. coli (EPEC) infected Caco-2 cells. Seglitide, a SST receptor (SSTR) 2 agonist, partly reversed the inhibiting action of EPEC on NHE8 expression, but SSTR5 agonist (L-817,818) had no effect on the expression of NHE8. Moreover, SST blocked the phosphorylation of p38 in EPEC-infected Caco-2 cells. Taken together, these results suggest that enhancement of intestinal NHE8 expression by SST could ameliorate the symptoms of mice with infectious colitis.

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References

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