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AMPK Enhances Enterocyte Migration and in vivo Intestinal Barrier Function
Author(s) -
Sun Xiaofei,
Xue Yansong,
Du Min,
Zhu Meijun
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1250.11
Subject(s) - enterocyte , ampk , barrier function , crypt , intestinal epithelium , paracellular transport , microbiology and biotechnology , chemistry , biology , endocrinology , medicine , epithelium , protein kinase a , small intestine , kinase , biochemistry , genetics , membrane , permeability (electromagnetism)
Impairment in gut epithelial integrity and barrier function is associated with many diseases, such as inflammatory bowel disease, obesity and diabetes. Inadequate mucosal wound healing is associated with defective enterocyte migration along the crypt‐villus axis. AMP‐activated protein kinase (AMPK), an energy sensor, has been suggested to mediate epithelial barrier function and enhances wound healing processes in cultured cells. However, the causal relationship between AMPK and intestinal barrier function remains underdetermined. The objective of this study was to provide direct evidence of the regulatory role of AMPK on intestinal barrier function and enterocyte migration in vivo . To test, mice with AMPKα1‐floxed gene were cross‐bred with VilCre mice to specifically knock out AMPKα1 gene in intestinal epithelial cells where villin is expressed. The migration of enterocyte and intestinal barrier function were compared between AMPK VilCre knockout (KO) and wild type (WT) male mice at the age of 2.5 months. AMPK VilCre KO mice had increased intestinal epithelial paracellular permeability to FITC‐dextran compared with WT mice, indicating a leaking gut. In addition, mucosal thickness and the migration of BrdU‐labeled enterocytes were decreased in AMPK VilCre KO mice. CDX2 is the key transcription factor committing cells to the intestinal epithelial lineage. Immunofluorescence staining further showed an abnormal expression pattern of CDX2 in AMPK VilCre mice, where CDX2 expression was extended from crypt to the middle of villi, while CDX2 expression resided along the epithelial cells in WT mice. Taken together, these data clearly show that AMPK is required for proper intestinal barrier function and enterocyte migration in vivo possibly through regulating cdx2 expression. Support or Funding Information NIH R15HD073864