Edema-induced intestinal dysfunction is mediated by STAT3 activation.
Increased signal transducer and activator of transcription 3 (STAT3) activation has been shown to be associated with intestinal dysfunction. The purpose of this study was to investigate the role of STAT3 in edema-induced intestinal dysfunction. Intestinal edema was induced in male Sprague-Dawley rats by a combination of mesenteric venous hypertension and fluid resuscitation (RESUS + VH). Resuscitation fluid alone (RESUS), venous hypertension alone (VH), and sham-operated rats (CONTROL) were used as controls. Edema development, STAT3 DNA binding activity, nuclear translocation, and phosphorylation were measured in rat distal small intestinal muscularis. A significant amount of edema development was measured in the RESUS + VH rats compared with CONTROL and VH from 30 min to 6 h after surgery. Edema developed in the RESUS group at 30 min postsurgery but resolved before 2 h postsurgery. A significant increase in STAT3 DNA binding activity was observed from 30 min to 6 h after surgery in the edematous RESUS + VH group compared with nonedematous CONTROL. In addition, a significant increase in STAT3 nuclear translocation and phosphorylation was measured in the RESUS + VH group 2 and 6 h after surgery. No significant increases in STAT3 activation were observed in either the RESUS or VH groups compared with CONTROL. Rats in both the RESUS + VH and CONTROL groups were pretreated with AG490 (5 mg/kg, i.p.) to block STAT3 activation. Signal transducer and activator of transcription 3 inhibition attenuated edema-induced decrease in intestinal contractile activity and myosin light chain phosphorylation. We conclude from these data that edema-induced decreases in intestinal contractile activity are mediated, at least in part, by STAT3 activation.
Uray
Karen S
KS
Division of Pediatric Surgery, Department of Surgery, University of Texas Medical School at Houston, 6431 Fannin, Houston, TX 77030, USA. karen.l.davis@uth.tmc.edu
Laine
Glen A
GA
Xue
Hasan
H
Allen
Steven J
SJ
Cox
Charles S
CS
D000818:Animals; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism* / Q000473:pathology; D007410:Intestinal Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000502:physiology*
D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat