Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke
Abstract Human brain samples were collected from 46 autopsy cases, including 23 fatal heat stroke cases and 23 age-matched controls. Nine candidate reference genes (PES1, POLR2A, IPO8, HMBS, SDHA, GAPDH, UBC, B2M, ACTB) were evaluated in the cerebral cortex of 10 forensic autopsy cases (5 heat strok...
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| Format: | Article |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01923-w |
| _version_ | 1818840547741138944 |
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| author | Yu Du Jing-Tao Xu Hong-Nian Jin Rui Zhao Dong Zhao Si-Hao Du Ye Xue Xiao-Li Xie Qi Wang |
| author_facet | Yu Du Jing-Tao Xu Hong-Nian Jin Rui Zhao Dong Zhao Si-Hao Du Ye Xue Xiao-Li Xie Qi Wang |
| author_sort | Yu Du |
| collection | DOAJ |
| description | Abstract Human brain samples were collected from 46 autopsy cases, including 23 fatal heat stroke cases and 23 age-matched controls. Nine candidate reference genes (PES1, POLR2A, IPO8, HMBS, SDHA, GAPDH, UBC, B2M, ACTB) were evaluated in the cerebral cortex of 10 forensic autopsy cases (5 heat stroke and 5 controls), using the geNorm module in qBaseplus software. SDHA, POLR2A, IPO8 and HMBS were identified as the most stable reference genes. Using these validated reference genes, mRNA expressions of Matrix metalloproteinases (MMPs, MMP2 and MMP9), Claudin5 (CLDN5), Occludin (OCLN), Zona occludens protein-1 (ZO1) and Aquaporins (AQPs, AQP1 and AQP4) in the cerebral cortex were examined. Relative mRNA quantification using Taqman real-time PCR assay demonstrated increased calibrated normalized relative quantity (CNRQ) values of MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke cases. Heat stroke cases showed an increase in brain water content, which was found to be positively correlated with MMP9, OCLN, ZO1 and CLDN5 mRNA. When using one conventional reference gene (GAPDH or ACTB) for normalization, no difference was detected between heat stroke and controls. In immunostaining, only AQP4 showed more intense staining in most heat stroke cases. The present study, for the first time, reports increased cerebral MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke and suggest a crucial role of reference gene selection when using postmortem human tissues. |
| first_indexed | 2024-12-19T04:11:56Z |
| format | Article |
| id | doaj.art-6fa29983c3624f518981de3f6774cfd0 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:11:56Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6fa29983c3624f518981de3f6774cfd02022-12-21T20:36:24ZengNature PortfolioScientific Reports2045-23222017-05-017111010.1038/s41598-017-01923-wIncreased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat strokeYu Du0Jing-Tao Xu1Hong-Nian Jin2Rui Zhao3Dong Zhao4Si-Hao Du5Ye Xue6Xiao-Li Xie7Qi Wang8Department of Forensic Medicine, National Police University of ChinaDepartment of Forensic Pathology, School of Forensic Medicine, Southern Medical UniversityForensic Science Centre of Guangdong Provincial Public Security DepartmentDepartment of Forensic Pathology, China Medical University School of Forensic MedicineCollaborative Innovation Center of Judicial Civilization, China; Key Laboratory of Evidence Science (China University of Political Science and Law), Ministry of EducationDepartment of Forensic Pathology, School of Forensic Medicine, Southern Medical UniversityDepartment of Forensic Pathology, School of Forensic Medicine, Southern Medical UniversityDepartment of Toxicology, School of Public Health, Southern Medical University, Guangdong Provincial Key Laboratory of Tropical Disease ResearchDepartment of Forensic Pathology, School of Forensic Medicine, Southern Medical UniversityAbstract Human brain samples were collected from 46 autopsy cases, including 23 fatal heat stroke cases and 23 age-matched controls. Nine candidate reference genes (PES1, POLR2A, IPO8, HMBS, SDHA, GAPDH, UBC, B2M, ACTB) were evaluated in the cerebral cortex of 10 forensic autopsy cases (5 heat stroke and 5 controls), using the geNorm module in qBaseplus software. SDHA, POLR2A, IPO8 and HMBS were identified as the most stable reference genes. Using these validated reference genes, mRNA expressions of Matrix metalloproteinases (MMPs, MMP2 and MMP9), Claudin5 (CLDN5), Occludin (OCLN), Zona occludens protein-1 (ZO1) and Aquaporins (AQPs, AQP1 and AQP4) in the cerebral cortex were examined. Relative mRNA quantification using Taqman real-time PCR assay demonstrated increased calibrated normalized relative quantity (CNRQ) values of MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke cases. Heat stroke cases showed an increase in brain water content, which was found to be positively correlated with MMP9, OCLN, ZO1 and CLDN5 mRNA. When using one conventional reference gene (GAPDH or ACTB) for normalization, no difference was detected between heat stroke and controls. In immunostaining, only AQP4 showed more intense staining in most heat stroke cases. The present study, for the first time, reports increased cerebral MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke and suggest a crucial role of reference gene selection when using postmortem human tissues.https://doi.org/10.1038/s41598-017-01923-w |
| spellingShingle | Yu Du Jing-Tao Xu Hong-Nian Jin Rui Zhao Dong Zhao Si-Hao Du Ye Xue Xiao-Li Xie Qi Wang Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke Scientific Reports |
| title | Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke |
| title_full | Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke |
| title_fullStr | Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke |
| title_full_unstemmed | Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke |
| title_short | Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke |
| title_sort | increased cerebral expressions of mmps cldn5 ocln zo1 and aqps are associated with brain edema following fatal heat stroke |
| url | https://doi.org/10.1038/s41598-017-01923-w |
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