RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site
Pyroptosis is involved in pulmonary hypertension (PH); however, whether this process is regulated by long non-coding RNAs (lncRNAs) is unclear. Some lncRNAs encode peptides; therefore, whether the regulation of pyroptosis in PH depends on lncRNAs themselves or their encoded peptides needs to be expl...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253122001469 |
| _version_ | 1828336110710816768 |
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| author | Yiying Li Junting Zhang Hanliang Sun Xiufeng Yu Yujie Chen Cui Ma Xiaodong Zheng Lixin Zhang Xijuan Zhao Yuan Jiang Wei Xin Shanshan Wang Jiye Hu Mingge Wang Daling Zhu |
| author_facet | Yiying Li Junting Zhang Hanliang Sun Xiufeng Yu Yujie Chen Cui Ma Xiaodong Zheng Lixin Zhang Xijuan Zhao Yuan Jiang Wei Xin Shanshan Wang Jiye Hu Mingge Wang Daling Zhu |
| author_sort | Yiying Li |
| collection | DOAJ |
| description | Pyroptosis is involved in pulmonary hypertension (PH); however, whether this process is regulated by long non-coding RNAs (lncRNAs) is unclear. Some lncRNAs encode peptides; therefore, whether the regulation of pyroptosis in PH depends on lncRNAs themselves or their encoded peptides needs to be explored. We aimed to characterize the role of the peptide RPS4XL encoded by lnc-Rps4l and its regulatory mechanisms during pyroptosis in PH. Transgenic mice overexpression of lnc-Rps4l was established to rescue the inhibition of hypoxia-induced pyroptosis in pulmonary artery smooth muscle cells (PASMCs). An adeno-associated virus 9 construct with a mutation in the open reading frame of lnc-Rps4l was used to verify that it could inhibit hypoxia-induced PASMCs pyroptosis through its encoded peptide RPS4XL. Glutathione S-transferase (GST) pull-down assays revealed that RPS4XL bound to HSC70, and microscale thermophoresis (MST) was performed to determine the HSC70 domain that interacted with RPS4XL. Through glycosylation site mutation, we confirmed that RPS4XL inhibited hypoxia-induced PASMCs pyroptosis by regulating HSC70 glycosylation. Our results showed that RPS4XL inhibits pyroptosis in a PH mouse model and hypoxic PASMCs by regulating HSC70 glycosylation. These results further clarify the important mechanism of vascular remodeling in PH pathology. |
| first_indexed | 2024-04-13T21:56:25Z |
| format | Article |
| id | doaj.art-66aabd8f3cbe4dfc992bfb575f1677ce |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-04-13T21:56:25Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-66aabd8f3cbe4dfc992bfb575f1677ce2022-12-22T02:28:15ZengElsevierMolecular Therapy: Nucleic Acids2162-25312022-06-0128920934RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation siteYiying Li0Junting Zhang1Hanliang Sun2Xiufeng Yu3Yujie Chen4Cui Ma5Xiaodong Zheng6Lixin Zhang7Xijuan Zhao8Yuan Jiang9Wei Xin10Shanshan Wang11Jiye Hu12Mingge Wang13Daling Zhu14Biopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaCentral Laboratory of Harbin Medical University (Daqing), Xinyang Road, Gaoxin District, Daqing 163319, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaCentral Laboratory of Harbin Medical University (Daqing), Xinyang Road, Gaoxin District, Daqing 163319, P.R. ChinaDepartment of Genetic And Cell Biology, Harbin Medical University (Daqing), Daqing 163319, P. R. ChinaCollege of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, Heilongjiang Province, ChinaCentral Laboratory of Harbin Medical University (Daqing), Xinyang Road, Gaoxin District, Daqing 163319, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaCollege of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, Heilongjiang Province, ChinaHarbin Medical University, Harbin 150081, Heilongjiang Province, P.R. ChinaBiopharmaceutical Key Laboratory of Heilongjiang Province, College of Pharmacy, Harbin Medical University, Harbin 150081, Heilongjiang Province, P.R. China; Central Laboratory of Harbin Medical University (Daqing), Xinyang Road, Gaoxin District, Daqing 163319, P.R. China; Corresponding author Daling Zhu, Central Laboratory of Harbin Medical University (Daqing), Xinyang Road, Gaoxin District, Daqing 163319, Heilongjiang, China.Pyroptosis is involved in pulmonary hypertension (PH); however, whether this process is regulated by long non-coding RNAs (lncRNAs) is unclear. Some lncRNAs encode peptides; therefore, whether the regulation of pyroptosis in PH depends on lncRNAs themselves or their encoded peptides needs to be explored. We aimed to characterize the role of the peptide RPS4XL encoded by lnc-Rps4l and its regulatory mechanisms during pyroptosis in PH. Transgenic mice overexpression of lnc-Rps4l was established to rescue the inhibition of hypoxia-induced pyroptosis in pulmonary artery smooth muscle cells (PASMCs). An adeno-associated virus 9 construct with a mutation in the open reading frame of lnc-Rps4l was used to verify that it could inhibit hypoxia-induced PASMCs pyroptosis through its encoded peptide RPS4XL. Glutathione S-transferase (GST) pull-down assays revealed that RPS4XL bound to HSC70, and microscale thermophoresis (MST) was performed to determine the HSC70 domain that interacted with RPS4XL. Through glycosylation site mutation, we confirmed that RPS4XL inhibited hypoxia-induced PASMCs pyroptosis by regulating HSC70 glycosylation. Our results showed that RPS4XL inhibits pyroptosis in a PH mouse model and hypoxic PASMCs by regulating HSC70 glycosylation. These results further clarify the important mechanism of vascular remodeling in PH pathology.http://www.sciencedirect.com/science/article/pii/S2162253122001469MT: Non-coding RNAspyroptosislnc-Rps4lRPS4XLpulmonary arterial hypertensionHSC70 |
| spellingShingle | Yiying Li Junting Zhang Hanliang Sun Xiufeng Yu Yujie Chen Cui Ma Xiaodong Zheng Lixin Zhang Xijuan Zhao Yuan Jiang Wei Xin Shanshan Wang Jiye Hu Mingge Wang Daling Zhu RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site Molecular Therapy: Nucleic Acids MT: Non-coding RNAs pyroptosis lnc-Rps4l RPS4XL pulmonary arterial hypertension HSC70 |
| title | RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site |
| title_full | RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site |
| title_fullStr | RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site |
| title_full_unstemmed | RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site |
| title_short | RPS4XL encoded by lnc-Rps4l inhibits hypoxia-induced pyroptosis by binding HSC70 glycosylation site |
| title_sort | rps4xl encoded by lnc rps4l inhibits hypoxia induced pyroptosis by binding hsc70 glycosylation site |
| topic | MT: Non-coding RNAs pyroptosis lnc-Rps4l RPS4XL pulmonary arterial hypertension HSC70 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253122001469 |
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