PMID- 24525021
OWN - NLM
STAT- MEDLINE
DCOM- 20140529
LR  - 20140402
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 306
IP  - 7
DP  - 2014 Apr 1
TI  - The acetylome regulators Hdac1 and Hdac2 differently modulate intestinal 
      epithelial cell dependent homeostatic responses in experimental colitis.
PG  - G594-605
LID - 10.1152/ajpgi.00393.2013 [doi]
AB  - Histone deacetylases (Hdac) remove acetyl groups from proteins, influencing 
      global and specific gene expression. Hdacs control inflammation, as shown by Hdac 
      inhibitor-dependent protection from dextran sulfate sodium (DSS)-induced murine 
      colitis. Although tissue-specific Hdac knockouts show redundant and specific 
      functions, little is known of their intestinal epithelial cell (IEC) role. We 
      have shown previously that dual Hdac1/Hdac2 IEC-specific loss disrupts cell 
      proliferation and determination, with decreased secretory cell numbers and 
      altered barrier function. We thus investigated how compound Hdac1/Hdac2 or Hdac2 
      IEC-specific deficiency alters the inflammatory response. Floxed Hdac1 and Hdac2 
      and villin-Cre mice were interbred. Compound Hdac1/Hdac2 IEC-deficient mice 
      showed chronic basal inflammation, with increased basal disease activity index 
      (DAI) and deregulated Reg gene colonic expression. DSS-treated dual Hdac1/Hdac2 
      IEC-deficient mice displayed increased DAI, histological score, intestinal 
      permeability, and inflammatory gene expression. In contrast to double knockouts, 
      Hdac2 IEC-specific loss did not affect IEC determination and growth, nor result 
      in chronic inflammation. However, Hdac2 disruption protected against DSS colitis, 
      as shown by decreased DAI, intestinal permeability and caspase-3 cleavage. Hdac2 
      IEC-specific deficient mice displayed increased expression of IEC gene subsets, 
      such as colonic antimicrobial Reg3b and Reg3g mRNAs, and decreased expression of 
      immune cell function-related genes. Our data show that Hdac1 and Hdac2 are 
      essential IEC homeostasis regulators. IEC-specific Hdac1 and Hdac2 may act as 
      epigenetic sensors and transmitters of environmental cues and regulate 
      IEC-mediated mucosal homeostatic and inflammatory responses. Different levels of 
      IEC Hdac activity may lead to positive or negative outcomes on intestinal 
      homeostasis during inflammation.
FAU - Turgeon, Naomie
AU  - Turgeon N
AD  - Departement d'anatomie et biologie cellulaire, Faculte de medecine et des 
      sciences de la sante, Pavillon de recherche appliquee sur le cancer, Universite 
      de Sherbrooke, Sherbrooke, Quebec, Canada.
FAU - Gagne, Julie Moore
AU  - Gagne JM
FAU - Blais, Mylene
AU  - Blais M
FAU - Gendron, Fernand-Pierre
AU  - Gendron FP
FAU - Boudreau, Francois
AU  - Boudreau F
FAU - Asselin, Claude
AU  - Asselin C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140213
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Inflammation Mediators)
RN  - 9042-14-2 (Dextran Sulfate)
RN  - EC 3.5.1.98 (Hdac1 protein, mouse)
RN  - EC 3.5.1.98 (Hdac2 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
RN  - EC 3.5.1.98 (Histone Deacetylase 2)
SB  - IM
MH  - Animals
MH  - Colitis/*enzymology/genetics/immunology/pathology
MH  - Colon/*enzymology/immunology/pathology
MH  - Dextran Sulfate
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic
MH  - Epithelial Cells/*enzymology/immunology/pathology
MH  - Gene Expression Regulation
MH  - Genotype
MH  - Histone Deacetylase 1/deficiency/genetics/*metabolism
MH  - Histone Deacetylase 2/deficiency/genetics/*metabolism
MH  - Homeostasis
MH  - Immunity, Mucosal
MH  - Inflammation Mediators/metabolism
MH  - Intestinal Mucosa/*enzymology/immunology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Permeability
MH  - Phenotype
MH  - Time Factors
OTO - NOTNLM
OT  - DSS
OT  - Hdac1
OT  - Hdac2
OT  - colitis
OT  - inflammation
OT  - intestinal epithelial cell
EDAT- 2014/02/15 06:00
MHDA- 2014/05/30 06:00
CRDT- 2014/02/15 06:00
PHST- 2014/02/15 06:00 [entrez]
PHST- 2014/02/15 06:00 [pubmed]
PHST- 2014/05/30 06:00 [medline]
AID - ajpgi.00393.2013 [pii]
AID - 10.1152/ajpgi.00393.2013 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2014 Apr 1;306(7):G594-605. doi: 
      10.1152/ajpgi.00393.2013. Epub 2014 Feb 13.