title: Intestinal mucosal barrier is injured by BMP2/4 via activation of NF-κB signals after ischemic reperfusion.
abstract: Intestinal ischemic reperfusion (I/R) can cause dysfunction of the intestinal mucosal barrier; however, the mechanism of the intestinal mucosal barrier dysfunction caused by I/R remains unclear. In this study, using intestinal epithelial cells under anaerobic cultivation and an in vivo rat intestinal I/R model, we found that hypoxia and I/R increased the expression of BMP2/4 and upregulated BMP type Ia receptor and BMP type II receptor expression. We also found that exogenous BMP2/4 can activate the ERK and AKT signaling pathways in rat small intestine (IEC-6) cells, thereby activating NF-κB signaling, which leads to increased levels of inflammatory factors, such as TNF-α and IL-6. Furthermore, recombinant BMP2/4 decreased the expression of the tight junction protein occludin via the activation of the NF-κB pathway; these effects were abolished by treatment with the BMP-specific antagonist noggin or the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). All these factors can destroy the intestinal mucosal barrier, thereby leading to weaker barrier function. On the basis of these data, we conclude that BMP2/4 may act as the pathogenic basis for intestinal mucosal barrier dysfunction when the intestines suffer an I/R injury. Our results provide background for the development pharmacologic interventions in the management of I/R injury.
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Binyu
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Center of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Kebin
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002460:Cell Line; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D015850:Interleukin-6; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid