Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway
It has been shown that non-coding RNAs (ncRNAs) play an important regulatory role in pathophysiological processes involving inflammation. The vascular endothelial growth factor A (VEGFA) gene also participates in the inflammatory process. However, the relationships between ncRNAs and VEGFA are curre...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00263/full |
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| author | Xiao-wen Cheng Xiao-wen Cheng Zhen-fei Chen Yu-feng Wan Qing Zhou Hua Wang Hua-qing Zhu |
| author_facet | Xiao-wen Cheng Xiao-wen Cheng Zhen-fei Chen Yu-feng Wan Qing Zhou Hua Wang Hua-qing Zhu |
| author_sort | Xiao-wen Cheng |
| collection | DOAJ |
| description | It has been shown that non-coding RNAs (ncRNAs) play an important regulatory role in pathophysiological processes involving inflammation. The vascular endothelial growth factor A (VEGFA) gene also participates in the inflammatory process. However, the relationships between ncRNAs and VEGFA are currently unclear. Here, this study was designed to determine the relationship between long non-coding RNA (lncRNA) H19, mircoRNA29b (miR-29b), and VEGFA in the development of diabetes mellitus (DM). We demonstrate that H19 is upregulated and miR-29b downregulated in individuals with DM and directly binds miR-29b. VEGFA is the target of miR-29b in the vascular endothelium of individuals with DM. We found that positive modulation of miR29b and inhibition of H19 and VEGFA significantly attenuates high glucose-induced endothelial inflammation and oxidative stress. We also found that the protein kinase B/endothelial nitric oxide synthase (AKT/eNOS) signal pathway in endothelial cells is activated through regulation of miR29b and H19 endogenous RNAs. We conclude that H19 suppression protects the endothelium against high glucose-induced inflammation and oxidative stress in endothelial cells by upregulation of miR-29b and downregulation of VEGFA through AKT/eNOS signal pathway activation. These results suggest a novel link between dysregulated ncRNA expression, inflammation, and the signaling pathway in the vascular endothelium of individuals with DM, indicating a promising strategy for preventing cardiovascular disease in such individuals. |
| first_indexed | 2024-12-11T06:41:36Z |
| format | Article |
| id | doaj.art-66b7feff6c3046b8b5739aa773efd454 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-11T06:41:36Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-66b7feff6c3046b8b5739aa773efd4542022-12-22T01:17:13ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-11-01710.3389/fcell.2019.00263491000Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase PathwayXiao-wen Cheng0Xiao-wen Cheng1Zhen-fei Chen2Yu-feng Wan3Qing Zhou4Hua Wang5Hua-qing Zhu6Department of Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University, Hefei, ChinaLaboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei, ChinaDepartment of Vasculocardiology, Hefei Hospital Affiliated to Anhui Medical University, Hefei, ChinaDepartment of Otolaryngology, The Affiliated Chaohu Hospital, Anhui Medical University, Hefei, ChinaLaboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei, ChinaDepartment of Oncology, The First Affiliated Hospital, Institute for Liver Disease, Anhui Medical University, Hefei, ChinaLaboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei, ChinaIt has been shown that non-coding RNAs (ncRNAs) play an important regulatory role in pathophysiological processes involving inflammation. The vascular endothelial growth factor A (VEGFA) gene also participates in the inflammatory process. However, the relationships between ncRNAs and VEGFA are currently unclear. Here, this study was designed to determine the relationship between long non-coding RNA (lncRNA) H19, mircoRNA29b (miR-29b), and VEGFA in the development of diabetes mellitus (DM). We demonstrate that H19 is upregulated and miR-29b downregulated in individuals with DM and directly binds miR-29b. VEGFA is the target of miR-29b in the vascular endothelium of individuals with DM. We found that positive modulation of miR29b and inhibition of H19 and VEGFA significantly attenuates high glucose-induced endothelial inflammation and oxidative stress. We also found that the protein kinase B/endothelial nitric oxide synthase (AKT/eNOS) signal pathway in endothelial cells is activated through regulation of miR29b and H19 endogenous RNAs. We conclude that H19 suppression protects the endothelium against high glucose-induced inflammation and oxidative stress in endothelial cells by upregulation of miR-29b and downregulation of VEGFA through AKT/eNOS signal pathway activation. These results suggest a novel link between dysregulated ncRNA expression, inflammation, and the signaling pathway in the vascular endothelium of individuals with DM, indicating a promising strategy for preventing cardiovascular disease in such individuals.https://www.frontiersin.org/article/10.3389/fcell.2019.00263/fulldiabetesH19inflammationmiRNA-29bvascular endothelial growth factor A |
| spellingShingle | Xiao-wen Cheng Xiao-wen Cheng Zhen-fei Chen Yu-feng Wan Qing Zhou Hua Wang Hua-qing Zhu Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway Frontiers in Cell and Developmental Biology diabetes H19 inflammation miRNA-29b vascular endothelial growth factor A |
| title | Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway |
| title_full | Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway |
| title_fullStr | Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway |
| title_full_unstemmed | Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway |
| title_short | Long Non-coding RNA H19 Suppression Protects the Endothelium Against Hyperglycemic-Induced Inflammation via Inhibiting Expression of miR-29b Target Gene Vascular Endothelial Growth Factor a Through Activation of the Protein Kinase B/Endothelial Nitric Oxide Synthase Pathway |
| title_sort | long non coding rna h19 suppression protects the endothelium against hyperglycemic induced inflammation via inhibiting expression of mir 29b target gene vascular endothelial growth factor a through activation of the protein kinase b endothelial nitric oxide synthase pathway |
| topic | diabetes H19 inflammation miRNA-29b vascular endothelial growth factor A |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00263/full |
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