The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model
Xue He,1–3 Tiao Li,1–3 Naixin Kang,1–3 Huihui Zeng,1–3 Siying Ren,1–3 Dandan Zong,1–3 Jinhua Li,1–3 Shan Cai,1–3 Ping Chen,1–3 Yan Chen1–3 1Department of Respiratory Medicine, The Second Xiangya Hosp...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2017-11-01
|
| Series: | International Journal of COPD |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-protective-effect-of-prmt6-overexpression-on-cigarette-smoke-extra-peer-reviewed-article-COPD |
| _version_ | 1828544544663142400 |
|---|---|
| author | He X Li T Kang N Zeng H Ren S Zong D Li J Cai S Chen P Chen Y |
| author_facet | He X Li T Kang N Zeng H Ren S Zong D Li J Cai S Chen P Chen Y |
| author_sort | He X |
| collection | DOAJ |
| description | Xue He,1–3 Tiao Li,1–3 Naixin Kang,1–3 Huihui Zeng,1–3 Siying Ren,1–3 Dandan Zong,1–3 Jinhua Li,1–3 Shan Cai,1–3 Ping Chen,1–3 Yan Chen1–3 1Department of Respiratory Medicine, The Second Xiangya Hospital, 2Research Unit of Respiratory Disease, 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China Background: Cigarette smoke exposure is the most common risk factor for emphysema, which is one of the major pathologies of COPD. Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that specially catalyzes dimethylation of R2 in histone H3 (H3R2me2a). H3R2me2a prevents trimethylation of H3K4 (H3K4me3), which is located in the transcription start sites of genes in mammalian genomes. We attempted to determine the expression of PRMT6 in human samples, and investigate whether the upregulation of PRMT6 expression can attenuate the development of cigarette smoke extract (CSE)-induced emphysema. Further experiments were performed to elucidate the molecular mechanisms involved.Materials and methods: Human lung tissues were obtained from patients undergoing pneumonectomy for benign pulmonary lesions. BALB/c mice were treated with lentiviral vectors intratracheally and injected with CSE three times. The protein expression of PRMT6, H3R2me2a, and H3K4me3 in human and mouse samples, as well as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and endothelial nitric oxide synthase (eNOS) in mice were detected in lung homogenates by Western blotting. The mRNA expression of cyclooxygenase-2, interleukin-6, Bcl-2, Bax, and eNOS in mice was measured by quantitative real-time polymerase chain reaction.Results: The expression of PRMT6 was significantly downregulated in the pulmonary parenchyma in smokers with COPD as well as in mice treated with CSE. Overexpression of PRMT6 was detected in the CSE + Lenti-PRMT6 group of mice, which reversed the expression of H3R2me2a and H3K4me3. Inflammation, apoptosis, and oxidative stress levels were severe in the CSE-treated emphysema mice compared with the control group, which was inhibited by the overexpression of PRMT6.Conclusion: The overexpression of PRMT6 might inhibit inflammation, apoptosis, and oxidative stress in CSE-induced emphysema mediated by H3R2me2a. Keywords: COPD, cigarette smoke extract, inflammation, apoptosis, oxidative stress, PRMT6 |
| first_indexed | 2024-12-12T02:32:39Z |
| format | Article |
| id | doaj.art-159328c8eb384089a10f421dbdd1cd04 |
| institution | Directory Open Access Journal |
| issn | 1178-2005 |
| language | English |
| last_indexed | 2024-12-12T02:32:39Z |
| publishDate | 2017-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of COPD |
| spelling | doaj.art-159328c8eb384089a10f421dbdd1cd042022-12-22T00:41:22ZengDove Medical PressInternational Journal of COPD1178-20052017-11-01Volume 123245325435445The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema modelHe XLi TKang NZeng HRen SZong DLi JCai SChen PChen YXue He,1–3 Tiao Li,1–3 Naixin Kang,1–3 Huihui Zeng,1–3 Siying Ren,1–3 Dandan Zong,1–3 Jinhua Li,1–3 Shan Cai,1–3 Ping Chen,1–3 Yan Chen1–3 1Department of Respiratory Medicine, The Second Xiangya Hospital, 2Research Unit of Respiratory Disease, 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, China Background: Cigarette smoke exposure is the most common risk factor for emphysema, which is one of the major pathologies of COPD. Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that specially catalyzes dimethylation of R2 in histone H3 (H3R2me2a). H3R2me2a prevents trimethylation of H3K4 (H3K4me3), which is located in the transcription start sites of genes in mammalian genomes. We attempted to determine the expression of PRMT6 in human samples, and investigate whether the upregulation of PRMT6 expression can attenuate the development of cigarette smoke extract (CSE)-induced emphysema. Further experiments were performed to elucidate the molecular mechanisms involved.Materials and methods: Human lung tissues were obtained from patients undergoing pneumonectomy for benign pulmonary lesions. BALB/c mice were treated with lentiviral vectors intratracheally and injected with CSE three times. The protein expression of PRMT6, H3R2me2a, and H3K4me3 in human and mouse samples, as well as B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and endothelial nitric oxide synthase (eNOS) in mice were detected in lung homogenates by Western blotting. The mRNA expression of cyclooxygenase-2, interleukin-6, Bcl-2, Bax, and eNOS in mice was measured by quantitative real-time polymerase chain reaction.Results: The expression of PRMT6 was significantly downregulated in the pulmonary parenchyma in smokers with COPD as well as in mice treated with CSE. Overexpression of PRMT6 was detected in the CSE + Lenti-PRMT6 group of mice, which reversed the expression of H3R2me2a and H3K4me3. Inflammation, apoptosis, and oxidative stress levels were severe in the CSE-treated emphysema mice compared with the control group, which was inhibited by the overexpression of PRMT6.Conclusion: The overexpression of PRMT6 might inhibit inflammation, apoptosis, and oxidative stress in CSE-induced emphysema mediated by H3R2me2a. Keywords: COPD, cigarette smoke extract, inflammation, apoptosis, oxidative stress, PRMT6https://www.dovepress.com/the-protective-effect-of-prmt6-overexpression-on-cigarette-smoke-extra-peer-reviewed-article-COPDchronic obstructive pulmonary diseasecigarette smoke extractinflammationapoptosisoxidative stress |
| spellingShingle | He X Li T Kang N Zeng H Ren S Zong D Li J Cai S Chen P Chen Y The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model International Journal of COPD chronic obstructive pulmonary disease cigarette smoke extract inflammation apoptosis oxidative stress |
| title | The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model |
| title_full | The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model |
| title_fullStr | The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model |
| title_full_unstemmed | The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model |
| title_short | The protective effect of PRMT6 overexpression on cigarette smoke extract-induced murine emphysema model |
| title_sort | protective effect of prmt6 overexpression on cigarette smoke extract induced murine emphysema model |
| topic | chronic obstructive pulmonary disease cigarette smoke extract inflammation apoptosis oxidative stress |
| url | https://www.dovepress.com/the-protective-effect-of-prmt6-overexpression-on-cigarette-smoke-extra-peer-reviewed-article-COPD |
| work_keys_str_mv | AT hex theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT lit theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT kangn theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT zengh theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT rens theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT zongd theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT lij theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT cais theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT chenp theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT cheny theprotectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT hex protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT lit protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT kangn protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT zengh protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT rens protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT zongd protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT lij protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT cais protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT chenp protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel AT cheny protectiveeffectofprmt6overexpressiononcigarettesmokeextractinducedmurineemphysemamodel |