Brain-derived neurotrophic factor modulates intestinal barrier by inhibiting intestinal epithelial cells apoptosis in mice.

摘要

We aimed to investigate the effects of brain-derived neurotrophicfactor (BDNF) on apoptosis of intestinal epithelial cells (IECs) andalterations of intestinal barrier integrity using BDNF knock-outmice model. Colonic tissues from BDNF+/+ mice and BDNF+/- micewere prepared for this study. The integrity of colonic mucosa wasevaluated by measuring trans-mucosa electrical resistance andtissue conductance in Ussing chamber. The colonic epithelialstructure was analyzed by transmission electron microscopy.Apoptosis involvement was determined with TUNEL staining,active caspase-3 immunostaining and Western blotting for theprotein expression of active caspase-3, Bax and Bcl-2. Theexpression levels and distribution of tight junction proteins wereevaluated by immunohistochemistry or Western blots. Comparedwith BDNF+/+ mice, BDNF+/- mice displayed impaired integrity andultrastructure alterations in their colonic mucosa, which wascharacterized by diminished microvilli, mitochondrial swelling andepithelial cells apoptosis. Altered intestinal barrier function waslinked to excessive apoptosis of IECs demonstrated by the higherproportion of TUNEL-positive apoptotic cells and enhancedcaspase activities in BDNF+/- mice. Increased expression of Baxand claudin-2 proteins and reduced Bcl-2 and tight junctionproteins (occludin, ZO-1 and claudin-1) expression were alsodetected in the colonic mucosa of BDNF+/- mice. BDNF may playa role in the maintenance of intestinal barrier integrity via itsanti-apoptotic properties.