Inhibition of lncRNA MEG3 protects renal tubular from hypoxia‐induced kidney injury in acute renal allografts by regulating miR‐181b/TNF‐α signaling pathway
Abstract Early damage to transplanted organs initiates excess inflammation that deteriorates existing injury, which is a leading cause of graft loss. Long noncoding RNAs (lncRNAs) are recently thought to play a significant role in cellular homeostasis during pathological process of kidney diseases. The aim of this study was to assess the function and mechanism of lncRNA, maternally expressed gene 3 (MEG3), on early renal allografts pathogenesis. Real‐time polymerase chain reaction (RT‐PCR) analysis found that the levels of MEG3 and miR‐181b‐5p were increased and decreased respectively in grafted kidney. The Western blot assay showed that TNF‐alpha was upregulated in the kidney and in HK‐2 cells. Administering MEG3‐specific small interfering RNA (siRNA) in mice silenced MEG3 expression and protected kidney renal allograft from injury. Bioinformatical analysis and luciferase assay indicated that MEG3 is a target of miR‐181b‐5p. MEG3 inhibition and overexpression promoted and suppressed miR‐181b‐5p levels respectively. In addition, Western blot and immunohistochemical staining suggested that decreased TNF‐alpha expression was observed in the kidney. In contrary to MEG3, miR181b overexpression attenuated hypoxia‐induced HK‐2 cell apoptosis, as well as suppressed hypoxia‐induced TNF‐alpha upregulation. In luciferase reporter assay, we confirmed that miR‐181b directly bound to the 3′‐untranslated region (3′‐UTR) of TNF‐alpha, thereby negatively regulating the TNF‐alpha expression. Our data suggested that MEG3 functions as a competing endogenous RNA for miR‐181b to regulate the TNF‐alpha expression in hypoxia‐induced kidney injury in acute renal allografts..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
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| Enthalten in: |
Journal of Cellular Biochemistry - 120(2019), 8, Seite 12822-12831 |
| Beteiligte Personen: |
Pang, Xinlu [VerfasserIn] |
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| Anmerkungen: |
© 2019 Wiley Periodicals, Inc. |
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| Umfang: |
10 |
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| doi: |
10.1002/jcb.28553 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
WLY007915845 |
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| 245 | 1 | 0 | |a Inhibition of lncRNA MEG3 protects renal tubular from hypoxia‐induced kidney injury in acute renal allografts by regulating miR‐181b/TNF‐α signaling pathway |
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| 520 | |a Abstract Early damage to transplanted organs initiates excess inflammation that deteriorates existing injury, which is a leading cause of graft loss. Long noncoding RNAs (lncRNAs) are recently thought to play a significant role in cellular homeostasis during pathological process of kidney diseases. The aim of this study was to assess the function and mechanism of lncRNA, maternally expressed gene 3 (MEG3), on early renal allografts pathogenesis. Real‐time polymerase chain reaction (RT‐PCR) analysis found that the levels of MEG3 and miR‐181b‐5p were increased and decreased respectively in grafted kidney. The Western blot assay showed that TNF‐alpha was upregulated in the kidney and in HK‐2 cells. Administering MEG3‐specific small interfering RNA (siRNA) in mice silenced MEG3 expression and protected kidney renal allograft from injury. Bioinformatical analysis and luciferase assay indicated that MEG3 is a target of miR‐181b‐5p. MEG3 inhibition and overexpression promoted and suppressed miR‐181b‐5p levels respectively. In addition, Western blot and immunohistochemical staining suggested that decreased TNF‐alpha expression was observed in the kidney. In contrary to MEG3, miR181b overexpression attenuated hypoxia‐induced HK‐2 cell apoptosis, as well as suppressed hypoxia‐induced TNF‐alpha upregulation. In luciferase reporter assay, we confirmed that miR‐181b directly bound to the 3′‐untranslated region (3′‐UTR) of TNF‐alpha, thereby negatively regulating the TNF‐alpha expression. Our data suggested that MEG3 functions as a competing endogenous RNA for miR‐181b to regulate the TNF‐alpha expression in hypoxia‐induced kidney injury in acute renal allografts. | ||
| 700 | 1 | |a Feng, Guiwen |4 aut | |
| 700 | 1 | |a Shang, Wenjun |4 aut | |
| 700 | 1 | |a Liu, Lei |4 aut | |
| 700 | 1 | |a Li, Jingfeng |4 aut | |
| 700 | 1 | |a Feng, Yonghua |4 aut | |
| 700 | 1 | |a Xie, Hongchang |4 aut | |
| 700 | 1 | |a Wang, Junxiang |4 aut | |
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