Medical College of Wisconsin
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Up-regulated cystic fibrosis transmembrane conductance regulator after anal stenosis in rats. J Pediatr Surg 2012 Mar;47(3):556-64

Date

03/20/2012

Pubmed ID

22424353

DOI

10.1016/j.jpedsurg.2011.09.041

Scopus ID

2-s2.0-84863265562 (requires institutional sign-in at Scopus site)

Abstract

BACKGROUND: The pathophysiology of fecal incontinence from fecal impaction and rectal distension is poorly understood. We hypothesize that fecal impaction elicits up-regulation of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated mucosal chloride channel.

METHODS: The anus was ligated to produce 75% stenosis in rats. Controls received ligation without inducing stenosis. 24 to 48 hours after ligation the colon was removed. Mucosal short-circuit current was measured by Ussing chamber. Western blot analysis was used to detect CFTR expression in the colonic mucosa. Ligated rats failed to defecate, whereas control rats stooled normally.

RESULTS: Ligated colons were markedly stool filled and dilated. Water content of feces was significantly increased to 66.5% ± 1.1% (P < .01, n = 12) 24 hours after ligation, vs controls (49.5 ± 5.2%, n = 12). Baseline short-circuit current was significantly increased in the distal (78.8 ± 7.4 μA/cm(2), n = 8, P < .01) and mid colon (24.5 ± 2.5 μA/cm(2), n = 8, P < .05) 24 hours after ligation, compared to control rats (12.5 ± 3.2 μA/cm2, n = 8). CFTR expression was significantly increased 24 hours after ligation in the mid and distal colon.

CONCLUSION: We observe that fecal impaction from anal ligation induces early compensatory up-regulation of CFTR, altering function from net absorption to net secretion in the mid and distal colon.

Author List

Ramprasad J, Sood M, Ludwig K, Takahashi T

Author

Kirk A. Ludwig MD Chief, Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Anal Canal
Animals
Biomarkers
Blotting, Western
Colon
Cystic Fibrosis Transmembrane Conductance Regulator
Fecal Impaction
Fecal Incontinence
Intestinal Mucosa
Ligation
Rats
Rats, Sprague-Dawley
Up-Regulation