Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice
Severe burn injury induces intestinal barrier dysfunction; however, the underlying mechanisms remain elusive. Our previous studies have shown that the intestinal epithelial tight junction (TJ) barrier dysfunction is associated with both endoplasmic reticulum (ER) stress and autophagy in severely bur...
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00606/full |
| _version_ | 1818862503639121920 |
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| author | Yalan Huang Yalan Huang Yu Wang Yanhai Feng Pei Wang Xiaochong He Hui Ren Fengjun Wang |
| author_facet | Yalan Huang Yalan Huang Yu Wang Yanhai Feng Pei Wang Xiaochong He Hui Ren Fengjun Wang |
| author_sort | Yalan Huang |
| collection | DOAJ |
| description | Severe burn injury induces intestinal barrier dysfunction; however, the underlying mechanisms remain elusive. Our previous studies have shown that the intestinal epithelial tight junction (TJ) barrier dysfunction is associated with both endoplasmic reticulum (ER) stress and autophagy in severely burned mice, but the precise role of ER stress and autophagy in the burn-induced intestinal TJ barrier dysfunction needs to be determined. In this study, female C57/BL6 mice were assigned randomly to either sham burn or 30% total body surface area (TBSA) full-thickness burn. The effects of ER stress and autophagy on the intestinal epithelial TJ barrier were validated by inducing or inhibiting both ER stress and autophagy in mice treated with sham burn or burn injury. The intestinal permeability, expression, and localization of TJ proteins, ER stress, and autophagy were assessed by physiological, morphological, and biochemical analyses. The results showed that inducing ER stress with tunicamycin or thapsigargin caused the activation of autophagy, the increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins in the sham-burned mice, and aggravated the burn-induced activation of autophagy, increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins. In contrast, inhibiting ER stress with 4-phenylbutyrate alleviated the burn-induced activation of autophagy, increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins. In addition, inducing autophagy with rapamycin resulted in the increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins in the sham-burned mice, and aggravated the burn-induced increase of intestinal permeability as well as the reduction and reorganization of TJ proteins. However, inhibiting autophagy with 3-methyladenine attenuated the burn-induced increase of intestinal permeability, as well as the reduction and reorganization TJ proteins. It is suggested that the ER stress-autophagy axis contributes to the intestinal epithelial TJ barrier dysfunction after severe burn injury. |
| first_indexed | 2024-12-19T10:00:54Z |
| format | Article |
| id | doaj.art-49ac838e80dd44c9b52e8c4265f263ab |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T10:00:54Z |
| publishDate | 2019-05-01 |
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| series | Frontiers in Physiology |
| spelling | doaj.art-49ac838e80dd44c9b52e8c4265f263ab2022-12-21T20:26:39ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-05-011010.3389/fphys.2019.00606453481Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in MiceYalan Huang0Yalan Huang1Yu Wang2Yanhai Feng3Pei Wang4Xiaochong He5Hui Ren6Fengjun Wang7School of Nursing, Third Military Medical University (Army Medical University), Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaDepartment of Gastroenterology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaSchool of Nursing, Third Military Medical University (Army Medical University), Chongqing, ChinaSchool of Nursing, Third Military Medical University (Army Medical University), Chongqing, ChinaState Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, ChinaSevere burn injury induces intestinal barrier dysfunction; however, the underlying mechanisms remain elusive. Our previous studies have shown that the intestinal epithelial tight junction (TJ) barrier dysfunction is associated with both endoplasmic reticulum (ER) stress and autophagy in severely burned mice, but the precise role of ER stress and autophagy in the burn-induced intestinal TJ barrier dysfunction needs to be determined. In this study, female C57/BL6 mice were assigned randomly to either sham burn or 30% total body surface area (TBSA) full-thickness burn. The effects of ER stress and autophagy on the intestinal epithelial TJ barrier were validated by inducing or inhibiting both ER stress and autophagy in mice treated with sham burn or burn injury. The intestinal permeability, expression, and localization of TJ proteins, ER stress, and autophagy were assessed by physiological, morphological, and biochemical analyses. The results showed that inducing ER stress with tunicamycin or thapsigargin caused the activation of autophagy, the increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins in the sham-burned mice, and aggravated the burn-induced activation of autophagy, increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins. In contrast, inhibiting ER stress with 4-phenylbutyrate alleviated the burn-induced activation of autophagy, increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins. In addition, inducing autophagy with rapamycin resulted in the increase of intestinal permeability, as well as the reduction and reorganization of TJ proteins in the sham-burned mice, and aggravated the burn-induced increase of intestinal permeability as well as the reduction and reorganization of TJ proteins. However, inhibiting autophagy with 3-methyladenine attenuated the burn-induced increase of intestinal permeability, as well as the reduction and reorganization TJ proteins. It is suggested that the ER stress-autophagy axis contributes to the intestinal epithelial TJ barrier dysfunction after severe burn injury.https://www.frontiersin.org/article/10.3389/fphys.2019.00606/fullburn injuryendoplasmic reticulum stressautophagytight junctionintestinal barrier dysfunction |
| spellingShingle | Yalan Huang Yalan Huang Yu Wang Yanhai Feng Pei Wang Xiaochong He Hui Ren Fengjun Wang Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice Frontiers in Physiology burn injury endoplasmic reticulum stress autophagy tight junction intestinal barrier dysfunction |
| title | Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice |
| title_full | Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice |
| title_fullStr | Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice |
| title_full_unstemmed | Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice |
| title_short | Role of Endoplasmic Reticulum Stress-Autophagy Axis in Severe Burn-Induced Intestinal Tight Junction Barrier Dysfunction in Mice |
| title_sort | role of endoplasmic reticulum stress autophagy axis in severe burn induced intestinal tight junction barrier dysfunction in mice |
| topic | burn injury endoplasmic reticulum stress autophagy tight junction intestinal barrier dysfunction |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00606/full |
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