HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/G933    most recent 00235.2005v2 00235.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Stehr, W. Articles by Warner, B. W. Search for Related Content PubMed PubMed Citation Articles by Stehr, W. Articles by Warner, B. W.

MUCOSAL BIOLOGY

Roles for p21^waf1/cip1 and p27^kip1 during the adaptation response to massive intestinal resection

¹Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati; and ²Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio

Submitted 23 May 2005 ; accepted in final form 23 November 2005

The magnitude of gut adaptation is a decisive factor in determining whether patients are able to live independent of parenteral nutrition after massive small bowel loss. We previously established that the cyclin-dependent kinase inhibitor (CDKI) p21^waf1/cip1 is necessary for enterocyte proliferation and a normal adaptation response. In the present study, we have further elucidated the role of this CDKI in the context of p27^kip1, another member of the Cip/Kip CDKI family. Small bowel resections (SBRs) or sham operations were performed in control (C57/BL6), p21^waf1/cip1-null, p27^kip1-null, and p21^waf1/cip1/p27^kip1 double-null mice. Morphological (villus height/crypt depth) alterations in the mucosa, the kinetics of enterocyte turnover (rates of enterocyte proliferation and apoptosis), and the protein expression of various cell cycle-regulatory proteins were recorded at various postoperative times. Enterocyte compartment-specific mRNA expression was investigated using laser capture microdissection. Resection-induced adaptation in control mice coincided with increased protein expression of p21^waf1/cip1 and decreased p27^kip1 within 3 days postoperatively. Identical changes in mRNA expression were detected in crypt but not in villus enterocytes. Adaptation occurred normally in control and p27^kip1-null mice; however, mice deficient in both p21^waf1/cip1 and p27^kip1 failed to increase baseline rates of enterocyte proliferation and adaptation. The expression of p21^waf1/cip1 protein and mRNA in the proliferative crypt compartment is necessary for resection-induced enterocyte proliferation and adaptation. The finding that deficient expression of p27^kip1 does not affect adaptation suggests that these similar CDKI family members display distinctive cellular functions during the complex process of intestinal adaptation.

cyclin-dependent kinase inhibitor; enterocyte proliferation; apoptosis