Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1
Abstract Sepsis is caused by microbial infection with high mortality worldwide, and characterized by multiple organ dysfunction and systemic inflammatory response. Previous study shows that miR‐181a level is increased during sepsis; however, the mechanism is still unknown. Therefore, to identify the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-03-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12310 |
| _version_ | 1818576727547314176 |
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| author | Zhu Wu Jie Chen Wei Zhao Chun‐Hua Zhuo Qiong Chen |
| author_facet | Zhu Wu Jie Chen Wei Zhao Chun‐Hua Zhuo Qiong Chen |
| author_sort | Zhu Wu |
| collection | DOAJ |
| description | Abstract Sepsis is caused by microbial infection with high mortality worldwide, and characterized by multiple organ dysfunction and systemic inflammatory response. Previous study shows that miR‐181a level is increased during sepsis; however, the mechanism is still unknown. Therefore, to identify the role of miR‐181a, lipopolysaccharide (LPS) was used to stimulate mouse peritoneal macrophages. The expressions of miR‐181a and SIRT1 were identified by QRT‐PCR, the levels of SIRT1, Nrf2, p‐P65, Bcl‐2 and Bax were detected by western blotting, the inflammatory cytokines TNF‐α, IL‐6 and IL‐1β were detected by ELISA, and the apoptosis was measured by flow cytometry. Bioinformatics and dual luciferase assay were used to unveil the binding sites and the targeted regulatory relationship of miR‐181a and SIRT1. LPS induced the upregulation of miR‐181a, downregulation of SIRT1 and a strong inflammatory response. In addition, LPS stimulation inhibited the expression of Nrf2 and activated the NF‐κB pathway. Moreover, the inhibition of miR‐181a attenuated inflammatory response and apoptosis during LPS stimulation, which was implemented by up‐regulating the expression of its target SIRT1. More fully, downregulation of SIRT1 by short hairpin interference resulted in a decreased expression of Nrf2, increased expression of p‐P65 and proinflammatory cytokines, and intensive apoptosis. Downregulation of miR‐181a could promote the expression of its target SIRT1, and then, attenuate inflammatory response and apoptosis via Nrf2 and NF‐κB signaling pathways during LPS treatment. miR‐181a can be a potential target of controlling the inflammatory response during sepsis and has important clinical significance for the treatment and rehabilitation of septic patients. |
| first_indexed | 2024-12-16T06:18:37Z |
| format | Article |
| id | doaj.art-f48db28f590b4b11b0ab03b4f18f9e59 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-12-16T06:18:37Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-f48db28f590b4b11b0ab03b4f18f9e592022-12-21T22:41:12ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502021-03-0137320020710.1002/kjm2.12310Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1Zhu Wu0Jie Chen1Wei Zhao2Chun‐Hua Zhuo3Qiong Chen4PICU, Department of Pediatrics, Zhujiang Hospital Southern Medical University Guangzhou ChinaSchool infirmary Guangzhou Vocational School of Finance and Economics Guangzhou ChinaPICU, Department of Pediatrics, Zhujiang Hospital Southern Medical University Guangzhou ChinaPICU, Department of Pediatrics, Zhujiang Hospital Southern Medical University Guangzhou ChinaCenter of Oral Implantology, Stomatological Hospital Southern Medical University Guangzhou ChinaAbstract Sepsis is caused by microbial infection with high mortality worldwide, and characterized by multiple organ dysfunction and systemic inflammatory response. Previous study shows that miR‐181a level is increased during sepsis; however, the mechanism is still unknown. Therefore, to identify the role of miR‐181a, lipopolysaccharide (LPS) was used to stimulate mouse peritoneal macrophages. The expressions of miR‐181a and SIRT1 were identified by QRT‐PCR, the levels of SIRT1, Nrf2, p‐P65, Bcl‐2 and Bax were detected by western blotting, the inflammatory cytokines TNF‐α, IL‐6 and IL‐1β were detected by ELISA, and the apoptosis was measured by flow cytometry. Bioinformatics and dual luciferase assay were used to unveil the binding sites and the targeted regulatory relationship of miR‐181a and SIRT1. LPS induced the upregulation of miR‐181a, downregulation of SIRT1 and a strong inflammatory response. In addition, LPS stimulation inhibited the expression of Nrf2 and activated the NF‐κB pathway. Moreover, the inhibition of miR‐181a attenuated inflammatory response and apoptosis during LPS stimulation, which was implemented by up‐regulating the expression of its target SIRT1. More fully, downregulation of SIRT1 by short hairpin interference resulted in a decreased expression of Nrf2, increased expression of p‐P65 and proinflammatory cytokines, and intensive apoptosis. Downregulation of miR‐181a could promote the expression of its target SIRT1, and then, attenuate inflammatory response and apoptosis via Nrf2 and NF‐κB signaling pathways during LPS treatment. miR‐181a can be a potential target of controlling the inflammatory response during sepsis and has important clinical significance for the treatment and rehabilitation of septic patients.https://doi.org/10.1002/kjm2.12310apoptosisinflammatory responsemiR‐181asepsisSIRT1 |
| spellingShingle | Zhu Wu Jie Chen Wei Zhao Chun‐Hua Zhuo Qiong Chen Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1 Kaohsiung Journal of Medical Sciences apoptosis inflammatory response miR‐181a sepsis SIRT1 |
| title | Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1 |
| title_full | Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1 |
| title_fullStr | Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1 |
| title_full_unstemmed | Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1 |
| title_short | Inhibition of miR‐181a attenuates sepsis‐induced inflammation and apoptosis by activating Nrf2 and inhibiting NF‐κB pathways via targeting SIRT1 |
| title_sort | inhibition of mir 181a attenuates sepsis induced inflammation and apoptosis by activating nrf2 and inhibiting nf κb pathways via targeting sirt1 |
| topic | apoptosis inflammatory response miR‐181a sepsis SIRT1 |
| url | https://doi.org/10.1002/kjm2.12310 |
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