Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma
Context Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). Objective To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. Materials and methods We recruited 10 healthy controls, 10 patients...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2022.2032205 |
| _version_ | 1818320779484332032 |
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| author | Yan Qian Yun Sun Yi Chen Zhengdao Mao Yujia Shi Di Wu Bin Gu Zhiguang Liu Qian Zhang |
| author_facet | Yan Qian Yun Sun Yi Chen Zhengdao Mao Yujia Shi Di Wu Bin Gu Zhiguang Liu Qian Zhang |
| author_sort | Yan Qian |
| collection | DOAJ |
| description | Context Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). Objective To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. Materials and methods We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. Results SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (−72%), PIK3R1 (−40%), and COL3A1 (−65%) compared with OVA + LPS. Conclusions Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA. |
| first_indexed | 2024-12-13T10:30:26Z |
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| id | doaj.art-95b3a96e59f54accad164850f2d13c5a |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-13T10:30:26Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-95b3a96e59f54accad164850f2d13c5a2022-12-21T23:50:53ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-0160134735810.1080/13880209.2022.20322052032205Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthmaYan Qian0Yun Sun1Yi Chen2Zhengdao Mao3Yujia Shi4Di Wu5Bin Gu6Zhiguang Liu7Qian Zhang8The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityThe Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityContext Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). Objective To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. Materials and methods We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. Results SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (−72%), PIK3R1 (−40%), and COL3A1 (−65%) compared with OVA + LPS. Conclusions Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA.http://dx.doi.org/10.1080/13880209.2022.2032205steroid insensitivitynuclear factor erythroid 2-related factor 2airway inflammation |
| spellingShingle | Yan Qian Yun Sun Yi Chen Zhengdao Mao Yujia Shi Di Wu Bin Gu Zhiguang Liu Qian Zhang Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma Pharmaceutical Biology steroid insensitivity nuclear factor erythroid 2-related factor 2 airway inflammation |
| title | Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma |
| title_full | Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma |
| title_fullStr | Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma |
| title_full_unstemmed | Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma |
| title_short | Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma |
| title_sort | nrf2 regulates downstream genes by targeting mir 29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid insensitive asthma |
| topic | steroid insensitivity nuclear factor erythroid 2-related factor 2 airway inflammation |
| url | http://dx.doi.org/10.1080/13880209.2022.2032205 |
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