Document Detail


Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome.
MedLine Citation:
PMID:  17307727     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Following the loss of functional small bowel surface area, the intestine undergoes a compensatory adaptive response. The observation that adaptation is inhibited in vitamin A-deficient rats following submassive intestinal resection suggested that vitamin A is required for this response and raised the possibility that exogenous vitamin A could augment adaptation. Therefore, to directly assess whether chronically administered retinoic acid could stimulate gut adaptation in a model of short bowel syndrome and to address the mechanisms of any such effects, Sprague-Dawley rats were implanted with controlled release retinoic acid or control pellets and then subjected to mid-small bowel or sham resections. At 2 wk postoperation, changes in gut morphology, crypt cell proliferation and apoptosis, enterocyte migration, the extracellular matrix, and gene expression were assessed. Retinoic acid had significant trophic effects in resected and sham-resected rats. Retinoic acid markedly inhibited apoptosis and stimulated crypt cell proliferation and enterocyte migration postresection. Data presented indicate that these proadaptive effects of retinoic acid may be mediated via changes in the extracellular matrix (e.g., by increasing collagen IV synthesis, decreasing E-cadherin expression, and reducing integrin beta(3) levels), via affects on Hedgehog signaling (e.g., by reducing expression of the Hedgehog receptors Ptch and Ptch2 and the Gli1 transcription factor), by increasing expression of Reg1 and Pap1, and by modulation of retinoid and peroxisome proliferator-activated receptor signaling pathways. These studies are the first to demonstrate that retinoic acid can significantly enhance intestinal adaptation and suggest it may be beneficial in patients with short bowel syndrome.
Authors:
Lihua Wang; Yuzhu Tang; Deborah C Rubin; Marc S Levin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-02-15
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  292     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-07     Completed Date:  2007-08-30     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G1559-69     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological / drug effects*,  genetics
Animals
Apoptosis / drug effects
Cell Movement / drug effects
Cell Proliferation / drug effects
Disease Models, Animal
Drug Implants
Enterocytes / drug effects,  pathology
Extracellular Matrix Proteins / metabolism
Gene Expression / drug effects
Hedgehog Proteins / metabolism
Intestine, Small / drug effects*,  metabolism,  pathology,  physiopathology,  surgery
Male
Peroxisome Proliferator-Activated Receptors / drug effects,  metabolism
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Receptors, Retinoic Acid / agonists*,  genetics,  metabolism
Short Bowel Syndrome / drug therapy*,  genetics,  metabolism,  pathology,  physiopathology
Signal Transduction / drug effects
Time Factors
Tretinoin / administration & dosage,  pharmacology*,  therapeutic use
Wnt Proteins / metabolism
beta Catenin / metabolism
Grant Support
ID/Acronym/Agency:
DK-46122/DK/NIDDK NIH HHS; DK-52574/DK/NIDDK NIH HHS; DK-56341/DK/NIDDK NIH HHS; DK-61216/DK/NIDDK NIH HHS; P30 DK056341/DK/NIDDK NIH HHS; P30 DK056341-06/DK/NIDDK NIH HHS; P30 DK056341-07/DK/NIDDK NIH HHS; R01 DK-50446/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Catnb protein, rat; 0/Drug Implants; 0/Extracellular Matrix Proteins; 0/Hedgehog Proteins; 0/Peroxisome Proliferator-Activated Receptors; 0/RNA, Messenger; 0/Receptors, Retinoic Acid; 0/Wnt Proteins; 0/beta Catenin; 5688UTC01R/Tretinoin
Comments/Corrections
Erratum In:
Am J Physiol Gastrointest Liver Physiol. 2007 Aug;293(2):G517-8

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