LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea
ABSTRACTLong noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of N...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Epigenetics |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2023.2293409 |
| _version_ | 1797352832194576384 |
|---|---|
| author | Kai Chen Baiqing Ou Quan Huang Daqing Deng Yi Xiang Fang Hu |
| author_facet | Kai Chen Baiqing Ou Quan Huang Daqing Deng Yi Xiang Fang Hu |
| author_sort | Kai Chen |
| collection | DOAJ |
| description | ABSTRACTLong noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4. |
| first_indexed | 2024-03-08T13:22:24Z |
| format | Article |
| id | doaj.art-3be3e49b46c44cf2ad4b11abc4e551a6 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-08T13:22:24Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-3be3e49b46c44cf2ad4b11abc4e551a62024-01-17T19:11:19ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2023.2293409LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoeaKai Chen0Baiqing Ou1Quan Huang2Daqing Deng3Yi Xiang4Fang Hu5Department of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, ChinaDepartment of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, ChinaDepartment of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, ChinaDepartment of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, ChinaDepartment of Cardiovascular Medicine Six Wards (Cardiovascular and Metabolic Diseases), Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, ChinaComprehensive internal medicine of Hunan Provincial People’s Hospital, Changsha, Hunan, ChinaABSTRACTLong noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.https://www.tandfonline.com/doi/10.1080/15592294.2023.2293409T2DM with OSAinflammationoxidative stresslncRNA NEAT1Apelin |
| spellingShingle | Kai Chen Baiqing Ou Quan Huang Daqing Deng Yi Xiang Fang Hu LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea Epigenetics T2DM with OSA inflammation oxidative stress lncRNA NEAT1 Apelin |
| title | LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea |
| title_full | LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea |
| title_fullStr | LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea |
| title_full_unstemmed | LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea |
| title_short | LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea |
| title_sort | lncrna neat1 aggravates human microvascular endothelial cell injury by inhibiting the apelin nrf2 ho 1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea |
| topic | T2DM with OSA inflammation oxidative stress lncRNA NEAT1 Apelin |
| url | https://www.tandfonline.com/doi/10.1080/15592294.2023.2293409 |
| work_keys_str_mv | AT kaichen lncrnaneat1aggravateshumanmicrovascularendothelialcellinjurybyinhibitingtheapelinnrf2ho1signallingpathwayintype2diabetesmellituswithobstructivesleepapnoea AT baiqingou lncrnaneat1aggravateshumanmicrovascularendothelialcellinjurybyinhibitingtheapelinnrf2ho1signallingpathwayintype2diabetesmellituswithobstructivesleepapnoea AT quanhuang lncrnaneat1aggravateshumanmicrovascularendothelialcellinjurybyinhibitingtheapelinnrf2ho1signallingpathwayintype2diabetesmellituswithobstructivesleepapnoea AT daqingdeng lncrnaneat1aggravateshumanmicrovascularendothelialcellinjurybyinhibitingtheapelinnrf2ho1signallingpathwayintype2diabetesmellituswithobstructivesleepapnoea AT yixiang lncrnaneat1aggravateshumanmicrovascularendothelialcellinjurybyinhibitingtheapelinnrf2ho1signallingpathwayintype2diabetesmellituswithobstructivesleepapnoea AT fanghu lncrnaneat1aggravateshumanmicrovascularendothelialcellinjurybyinhibitingtheapelinnrf2ho1signallingpathwayintype2diabetesmellituswithobstructivesleepapnoea |