Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion
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 intestina...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/901530 |
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| _version_ | 1832566809135415296 |
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| author | Kang Chen Wei Xie Binyu Luo Weidong Xiao Daniel H. Teitelbaum Hua Yang Kebin Zhang Chaojun Zhang |
| author_facet | Kang Chen Wei Xie Binyu Luo Weidong Xiao Daniel H. Teitelbaum Hua Yang Kebin Zhang Chaojun Zhang |
| author_sort | Kang Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3a6d3244b3264fd2b4661446e96ef49a |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3a6d3244b3264fd2b4661446e96ef49a2025-02-03T01:02:59ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/901530901530Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic ReperfusionKang Chen0Wei Xie1Binyu Luo2Weidong Xiao3Daniel H. Teitelbaum4Hua Yang5Kebin Zhang6Chaojun Zhang7Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaCenter of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaDepartment of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaDepartment of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaDepartment of Surgery, University of Michigan, Ann Arbor, MI 48109, USADepartment of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaCenter of Medical Experiment & Technology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaDepartment of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, ChinaIntestinal 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.http://dx.doi.org/10.1155/2014/901530 |
| spellingShingle | Kang Chen Wei Xie Binyu Luo Weidong Xiao Daniel H. Teitelbaum Hua Yang Kebin Zhang Chaojun Zhang Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion Mediators of Inflammation |
| title | Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion |
| title_full | Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion |
| title_fullStr | Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion |
| title_full_unstemmed | Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion |
| title_short | Intestinal Mucosal Barrier Is Injured by BMP2/4 via Activation of NF-κB Signals after Ischemic Reperfusion |
| title_sort | intestinal mucosal barrier is injured by bmp2 4 via activation of nf κb signals after ischemic reperfusion |
| url | http://dx.doi.org/10.1155/2014/901530 |
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