Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway
<b>Aims:</b> Annexin A5 (ANXA5) exhibited potent antithrombotic, antiapoptotic, and anti-inflammatory properties in a previous study. The role of ANXA5 in traumatic brain injury (TBI)-induced intestinal injury is not fully known. <b>Main methods:</b> Recombinant human ANXA5 (...
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MDPI AG
2022-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/18/5755 |
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| author | Hejun Zhang Yalong Gao Tuo Li Fanjian Li Ruilong Peng Cong Wang Shu Zhang Jianning Zhang |
| author_facet | Hejun Zhang Yalong Gao Tuo Li Fanjian Li Ruilong Peng Cong Wang Shu Zhang Jianning Zhang |
| author_sort | Hejun Zhang |
| collection | DOAJ |
| description | <b>Aims:</b> Annexin A5 (ANXA5) exhibited potent antithrombotic, antiapoptotic, and anti-inflammatory properties in a previous study. The role of ANXA5 in traumatic brain injury (TBI)-induced intestinal injury is not fully known. <b>Main methods:</b> Recombinant human ANXA5 (50 µg/kg) or vehicle (PBS) was administered to mice via the tail vein 30 min after TBI. Mouse intestine tissue was gathered for hematoxylin and eosin staining 0.5 d, 1 d, 2 d, and 7 d after modeling. Intestinal Western blotting, immunofluorescence, TdT-mediated dUTP nick-end labeling staining, and enzyme-linked immunosorbent assays were performed 2 days after TBI. A series of kits were used to assess lipid peroxide indicators such as malonaldehyde, superoxide dismutase activity, and catalase activity. <b>Key findings:</b> ANXA5 treatment improved the TBI-induced intestinal mucosa injury at different timepoints and significantly increased the body weight. It significantly reduced apoptosis and matrix metalloproteinase-9 and inhibited the degradation of tight-junction-associated protein in the small intestine. ANXA5 treatment improved intestinal inflammation by regulating inflammation-associated factors. It also mitigated the lipid peroxidation products 4-HNE, 8-OHDG, and malonaldehyde, and enhanced the activity of the antioxidant enzymes, superoxide dismutase and catalase. Lastly, ANXA5 significantly enhanced nuclear factor E2-related factor 2 (Nrf2) and hemeoxygenase-1, and decreased high mobility group box 1 (HMGB1). <b>Significance:</b> Collectively, the results suggest that ANXA5 inhibits TBI-induced intestinal injury by restraining oxidative stress and inflammatory responses. The mechanisms involved sparking the Nrf2/hemeoxygenase-1-induced antioxidant system and suppressing the HMGB1 pathway. ANXA5 may be an attractive therapeutic candidate for protecting against TBI-induced intestinal injury. |
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| last_indexed | 2024-03-09T23:03:26Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-e7a70bf09b7c422f8f48d1602dadde7e2023-11-23T17:58:22ZengMDPI AGMolecules1420-30492022-09-012718575510.3390/molecules27185755Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 PathwayHejun Zhang0Yalong Gao1Tuo Li2Fanjian Li3Ruilong Peng4Cong Wang5Shu Zhang6Jianning Zhang7Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, ChinaDepartment of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300000, China<b>Aims:</b> Annexin A5 (ANXA5) exhibited potent antithrombotic, antiapoptotic, and anti-inflammatory properties in a previous study. The role of ANXA5 in traumatic brain injury (TBI)-induced intestinal injury is not fully known. <b>Main methods:</b> Recombinant human ANXA5 (50 µg/kg) or vehicle (PBS) was administered to mice via the tail vein 30 min after TBI. Mouse intestine tissue was gathered for hematoxylin and eosin staining 0.5 d, 1 d, 2 d, and 7 d after modeling. Intestinal Western blotting, immunofluorescence, TdT-mediated dUTP nick-end labeling staining, and enzyme-linked immunosorbent assays were performed 2 days after TBI. A series of kits were used to assess lipid peroxide indicators such as malonaldehyde, superoxide dismutase activity, and catalase activity. <b>Key findings:</b> ANXA5 treatment improved the TBI-induced intestinal mucosa injury at different timepoints and significantly increased the body weight. It significantly reduced apoptosis and matrix metalloproteinase-9 and inhibited the degradation of tight-junction-associated protein in the small intestine. ANXA5 treatment improved intestinal inflammation by regulating inflammation-associated factors. It also mitigated the lipid peroxidation products 4-HNE, 8-OHDG, and malonaldehyde, and enhanced the activity of the antioxidant enzymes, superoxide dismutase and catalase. Lastly, ANXA5 significantly enhanced nuclear factor E2-related factor 2 (Nrf2) and hemeoxygenase-1, and decreased high mobility group box 1 (HMGB1). <b>Significance:</b> Collectively, the results suggest that ANXA5 inhibits TBI-induced intestinal injury by restraining oxidative stress and inflammatory responses. The mechanisms involved sparking the Nrf2/hemeoxygenase-1-induced antioxidant system and suppressing the HMGB1 pathway. ANXA5 may be an attractive therapeutic candidate for protecting against TBI-induced intestinal injury.https://www.mdpi.com/1420-3049/27/18/5755ANXA5HMGB1/Nrf2/HO-1inflammatoryintestineoxidative stress |
| spellingShingle | Hejun Zhang Yalong Gao Tuo Li Fanjian Li Ruilong Peng Cong Wang Shu Zhang Jianning Zhang Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway Molecules ANXA5 HMGB1/Nrf2/HO-1 inflammatory intestine oxidative stress |
| title | Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway |
| title_full | Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway |
| title_fullStr | Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway |
| title_full_unstemmed | Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway |
| title_short | Recombinant Human Annexin A5 Alleviated Traumatic-Brain-Injury Induced Intestinal Injury by Regulating the Nrf2/HO-1/HMGB1 Pathway |
| title_sort | recombinant human annexin a5 alleviated traumatic brain injury induced intestinal injury by regulating the nrf2 ho 1 hmgb1 pathway |
| topic | ANXA5 HMGB1/Nrf2/HO-1 inflammatory intestine oxidative stress |
| url | https://www.mdpi.com/1420-3049/27/18/5755 |
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