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Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p
Acute kidney injury (AKI) is increasingly identified as a crucial risk factor for progression to CKD. However, the factors governing AKI to CKD progression remain largely unknown. By high-throughput RNA sequencing, we found that Neat1_2, a transcript variant of Neat1, was upregulated in 40-min ische...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552914/ https://www.ncbi.nlm.nih.gov/pubmed/35619557 http://dx.doi.org/10.1016/j.ymthe.2022.05.019 |
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author | Ma, Tongtong Li, Hongwei Liu, Hui Peng, Yili Lin, Tong Deng, Zhiya Jia, Nan Chen, Zhongqing Wang, Peng |
author_facet | Ma, Tongtong Li, Hongwei Liu, Hui Peng, Yili Lin, Tong Deng, Zhiya Jia, Nan Chen, Zhongqing Wang, Peng |
author_sort | Ma, Tongtong |
collection | PubMed |
description | Acute kidney injury (AKI) is increasingly identified as a crucial risk factor for progression to CKD. However, the factors governing AKI to CKD progression remain largely unknown. By high-throughput RNA sequencing, we found that Neat1_2, a transcript variant of Neat1, was upregulated in 40-min ischemia/reperfusion injury (IRI), which resulted in the development of renal fibrotic lesions. The upregulation of Neat1_2 in hypoxia-treated TECs was attributed to p53 transcriptional regulation. Gain- and loss-of-function studies, both in vitro and in vivo, demonstrated that Neat1_2 promoted apoptosis of injured TECs induced by IRI and caused tubulointerstitial inflammation and fibrosis. Mechanistically, Neat1_2 shares miRNA response elements with FADD, CASP-8, and CASP-3. Neat1_2 competitively binds to miR-129-5p and prevents miR-129-5p from decreasing the levels of FADD, CASP-8, and CASP-3, and ultimately facilitates TEC apoptosis. Increased expression of Neat1_2 associated with kidney injury and TEC apoptosis was recapitulated in human AKI, highlighting its clinical relevance. These findings suggest that preventing TEC apoptosis by hindering Neat1_2 expression may be a potential therapeutic strategy for AKI to CKD progression. |
format | Online Article Text |
id | pubmed-9552914 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-95529142023-10-05 Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p Ma, Tongtong Li, Hongwei Liu, Hui Peng, Yili Lin, Tong Deng, Zhiya Jia, Nan Chen, Zhongqing Wang, Peng Mol Ther Original Article Acute kidney injury (AKI) is increasingly identified as a crucial risk factor for progression to CKD. However, the factors governing AKI to CKD progression remain largely unknown. By high-throughput RNA sequencing, we found that Neat1_2, a transcript variant of Neat1, was upregulated in 40-min ischemia/reperfusion injury (IRI), which resulted in the development of renal fibrotic lesions. The upregulation of Neat1_2 in hypoxia-treated TECs was attributed to p53 transcriptional regulation. Gain- and loss-of-function studies, both in vitro and in vivo, demonstrated that Neat1_2 promoted apoptosis of injured TECs induced by IRI and caused tubulointerstitial inflammation and fibrosis. Mechanistically, Neat1_2 shares miRNA response elements with FADD, CASP-8, and CASP-3. Neat1_2 competitively binds to miR-129-5p and prevents miR-129-5p from decreasing the levels of FADD, CASP-8, and CASP-3, and ultimately facilitates TEC apoptosis. Increased expression of Neat1_2 associated with kidney injury and TEC apoptosis was recapitulated in human AKI, highlighting its clinical relevance. These findings suggest that preventing TEC apoptosis by hindering Neat1_2 expression may be a potential therapeutic strategy for AKI to CKD progression. American Society of Gene & Cell Therapy 2022-10-05 2022-05-26 /pmc/articles/PMC9552914/ /pubmed/35619557 http://dx.doi.org/10.1016/j.ymthe.2022.05.019 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Ma, Tongtong Li, Hongwei Liu, Hui Peng, Yili Lin, Tong Deng, Zhiya Jia, Nan Chen, Zhongqing Wang, Peng Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p |
title | Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p |
title_full | Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p |
title_fullStr | Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p |
title_full_unstemmed | Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p |
title_short | Neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering miR-129-5p |
title_sort | neat1 promotes acute kidney injury to chronic kidney disease by facilitating tubular epithelial cells apoptosis via sequestering mir-129-5p |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552914/ https://www.ncbi.nlm.nih.gov/pubmed/35619557 http://dx.doi.org/10.1016/j.ymthe.2022.05.019 |
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