PMID- 29527912 OWN - NLM STAT- MEDLINE DCOM- 20181126 LR - 20190612 IS - 1802-9973 (Electronic) IS - 0862-8408 (Linking) VI - 67 IP - 3 DP - 2018 Jul 17 TI - Brain-derived neurotrophic factor modulates intestinal barrier by inhibiting intestinal epithelial cells apoptosis in mice. PG - 475-485 AB - We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF(+/+) mice and BDNF(+/-) mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy. Apoptosis involvement was determined with TUNEL staining, active caspase-3 immunostaining and Western blotting for the protein expression of active caspase-3, Bax and Bcl-2. The expression levels and distribution of tight junction proteins were evaluated by immunohistochemistry or Western blots. Compared with BDNF(+/+) mice, BDNF(+/-) mice displayed impaired integrity and ultrastructure alterations in their colonic mucosa, which was characterized by diminished microvilli, mitochondrial swelling and epithelial cells apoptosis. Altered intestinal barrier function was linked to excessive apoptosis of IECs demonstrated by the higher proportion of TUNEL-positive apoptotic cells and enhanced caspase activities in BDNF(+/-) mice. Increased expression of Bax and claudin-2 proteins and reduced Bcl-2 and tight junction proteins (occludin, ZO-1 and claudin-1) expression were also detected in the colonic mucosa of BDNF(+/-) mice. BDNF may play a role in the maintenance of intestinal barrier integrity via its anti-apoptotic properties. FAU - Zhao, D Y AU - Zhao DY AD - Department of Gastroenterology, Puyang Oilfield General Hospital, Puyang, China; Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, P.R. China. yuyanbo2000@126.com. FAU - Zhang, W X AU - Zhang WX FAU - Qi, Q Q AU - Qi QQ FAU - Long, X AU - Long X FAU - Li, X AU - Li X FAU - Yu, Y B AU - Yu YB FAU - Zuo, X L AU - Zuo XL LA - eng PT - Journal Article DEP - 20180312 PL - Czech Republic TA - Physiol Res JT - Physiological research JID - 9112413 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Tight Junction Proteins) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - *Apoptosis MH - Brain-Derived Neurotrophic Factor/*physiology MH - Caspase 3/metabolism MH - Epithelial Cells/*physiology MH - Female MH - Intestinal Mucosa/*metabolism/ultrastructure MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Tight Junction Proteins/metabolism EDAT- 2018/03/13 06:00 MHDA- 2018/11/27 06:00 CRDT- 2018/03/13 06:00 PHST- 2018/03/13 06:00 [pubmed] PHST- 2018/11/27 06:00 [medline] PHST- 2018/03/13 06:00 [entrez] AID - 933641 [pii] AID - 10.33549/physiolres.933641 [doi] PST - ppublish SO - Physiol Res. 2018 Jul 17;67(3):475-485. doi: 10.33549/physiolres.933641. Epub 2018 Mar 12.