MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI
Fibroblast growth factor-inducible molecule 14 (Fn14) plays a principal role in triggering tubular damage during septic acute kidney injury (AKI). Here, we explore the mechanism underlying Fn14 deregulation in septic AKI. We identify Fn14 as a bona fide target of miR-19a, which directly binds to 3′...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Analytical Cellular Pathology |
| Online Access: | http://dx.doi.org/10.1155/2020/2894650 |
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| author | Jun Hong Bang-Chuan Hu Liang Xu Yang Zheng Zi-Qiang Shao Run Zhang Xiang-Hong Yang Ren-Hua Sun Shi-Jing Mo |
| author_facet | Jun Hong Bang-Chuan Hu Liang Xu Yang Zheng Zi-Qiang Shao Run Zhang Xiang-Hong Yang Ren-Hua Sun Shi-Jing Mo |
| author_sort | Jun Hong |
| collection | DOAJ |
| description | Fibroblast growth factor-inducible molecule 14 (Fn14) plays a principal role in triggering tubular damage during septic acute kidney injury (AKI). Here, we explore the mechanism underlying Fn14 deregulation in septic AKI. We identify Fn14 as a bona fide target of miR-19a, which directly binds to 3′ UTR of Fn14 for repression independent of cylindromatosis (CYLD), the deubiquitinase (DUB) downstream of miR-19a, and thereby antagonizes the LPS-induced tubular cell apoptosis. Genetic ablation of Fn14, but not of CYLD, abolishes the ability of miR-19a to antagonize the tubular apoptosis by lipopolysaccharide (LPS). In mice, systemic delivery of miR-19a confers protection against septic AKI. Our findings implicate that miR-19a may serve as a promising therapeutic candidate in the prevention of septic AKI. |
| format | Article |
| id | doaj-art-5c4e2cd7eafb41ef840118581af1cbcd |
| institution | Kabale University |
| issn | 2210-7177 2210-7185 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Analytical Cellular Pathology |
| spelling | doaj-art-5c4e2cd7eafb41ef840118581af1cbcd2025-02-03T06:45:53ZengWileyAnalytical Cellular Pathology2210-71772210-71852020-01-01202010.1155/2020/28946502894650MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKIJun Hong0Bang-Chuan Hu1Liang Xu2Yang Zheng3Zi-Qiang Shao4Run Zhang5Xiang-Hong Yang6Ren-Hua Sun7Shi-Jing Mo8Department of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaDepartment of Intensive Care Unit, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014 Zhejiang, ChinaFibroblast growth factor-inducible molecule 14 (Fn14) plays a principal role in triggering tubular damage during septic acute kidney injury (AKI). Here, we explore the mechanism underlying Fn14 deregulation in septic AKI. We identify Fn14 as a bona fide target of miR-19a, which directly binds to 3′ UTR of Fn14 for repression independent of cylindromatosis (CYLD), the deubiquitinase (DUB) downstream of miR-19a, and thereby antagonizes the LPS-induced tubular cell apoptosis. Genetic ablation of Fn14, but not of CYLD, abolishes the ability of miR-19a to antagonize the tubular apoptosis by lipopolysaccharide (LPS). In mice, systemic delivery of miR-19a confers protection against septic AKI. Our findings implicate that miR-19a may serve as a promising therapeutic candidate in the prevention of septic AKI.http://dx.doi.org/10.1155/2020/2894650 |
| spellingShingle | Jun Hong Bang-Chuan Hu Liang Xu Yang Zheng Zi-Qiang Shao Run Zhang Xiang-Hong Yang Ren-Hua Sun Shi-Jing Mo MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI Analytical Cellular Pathology |
| title | MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI |
| title_full | MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI |
| title_fullStr | MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI |
| title_full_unstemmed | MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI |
| title_short | MicroRNA-19a Targets Fibroblast Growth Factor-Inducible Molecule 14 and Prevents Tubular Damage in Septic AKI |
| title_sort | microrna 19a targets fibroblast growth factor inducible molecule 14 and prevents tubular damage in septic aki |
| url | http://dx.doi.org/10.1155/2020/2894650 |
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