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tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA
Podocyte injury plays a key role in the production of proteinuria and is closely related to the progression of chronic kidney disease (CKD). Alleviating podocyte injury is beneficial to prevent the occurrence and development of CKD. tRNA-derived RNA fragments (tRFs) are associated with podocytes inj...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586663/ https://www.ncbi.nlm.nih.gov/pubmed/37856510 http://dx.doi.org/10.1371/journal.pone.0293043 |
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author | Gao, Xiaoqing Qiao, Yunyang Li, Shanwen Shi, Huimin Qu, Gaoting Ji, Jialing Gan, Weihua Zhang, Aiqing |
author_facet | Gao, Xiaoqing Qiao, Yunyang Li, Shanwen Shi, Huimin Qu, Gaoting Ji, Jialing Gan, Weihua Zhang, Aiqing |
author_sort | Gao, Xiaoqing |
collection | PubMed |
description | Podocyte injury plays a key role in the production of proteinuria and is closely related to the progression of chronic kidney disease (CKD). Alleviating podocyte injury is beneficial to prevent the occurrence and development of CKD. tRNA-derived RNA fragments (tRFs) are associated with podocytes injury processes such as protein binding, cell adhesion, synapses, the actin cytoskeleton. Our previous data showed that tRF-003634 tightly correlated with podocyte injury, while its effect remains unclear. This study aimed to investigate the role of tRF-003634 in podocyte injury and the potential mechanisms. The expression level of tRF-003634, nephrin, podocin and tRF-003634 targeted toll-like receptor 4 (TLR4) in podocytes and kidney tissues were examined by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The biochemical indices were monitored and renal pathological changes were assessed by hematoxylin and eosin PAS staining. Furthermore, potential target genes of tRF-003634 were screened using high-throughput mRNA sequencing, and then confirmed by RNA pulse-chase analysis. The results showed that tRF-003634 was downregulated in adriamycin (Adr)-induced podocyte injury. Overexpression of tRF-003634 increased the expression of nephrin and podocin in vivo and in vitro and alleviated podocyte injury. Meanwhile, overexpression of tRF-003634 alleviated proteinuria and renal pathological damage. In addition, high-throughput sequencing after overexpression of tRF-003634 showed that TLR4 might be a downstream target gene. tRF-003634 can alleviate podocyte injury by reducing the stability of TLR4 mRNA, possibly by competing with TLR4 mRNA to bind to YTH domain-containing protein 1 (YTHDC1). In conclusion, tRF-003634 was underexpressed in Adr-induced podocyte injury, and its overexpression alleviated podocyte injury in vitro and in vivo by reducing the stability of TLR4 mRNA. |
format | Online Article Text |
id | pubmed-10586663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105866632023-10-20 tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA Gao, Xiaoqing Qiao, Yunyang Li, Shanwen Shi, Huimin Qu, Gaoting Ji, Jialing Gan, Weihua Zhang, Aiqing PLoS One Research Article Podocyte injury plays a key role in the production of proteinuria and is closely related to the progression of chronic kidney disease (CKD). Alleviating podocyte injury is beneficial to prevent the occurrence and development of CKD. tRNA-derived RNA fragments (tRFs) are associated with podocytes injury processes such as protein binding, cell adhesion, synapses, the actin cytoskeleton. Our previous data showed that tRF-003634 tightly correlated with podocyte injury, while its effect remains unclear. This study aimed to investigate the role of tRF-003634 in podocyte injury and the potential mechanisms. The expression level of tRF-003634, nephrin, podocin and tRF-003634 targeted toll-like receptor 4 (TLR4) in podocytes and kidney tissues were examined by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry. The biochemical indices were monitored and renal pathological changes were assessed by hematoxylin and eosin PAS staining. Furthermore, potential target genes of tRF-003634 were screened using high-throughput mRNA sequencing, and then confirmed by RNA pulse-chase analysis. The results showed that tRF-003634 was downregulated in adriamycin (Adr)-induced podocyte injury. Overexpression of tRF-003634 increased the expression of nephrin and podocin in vivo and in vitro and alleviated podocyte injury. Meanwhile, overexpression of tRF-003634 alleviated proteinuria and renal pathological damage. In addition, high-throughput sequencing after overexpression of tRF-003634 showed that TLR4 might be a downstream target gene. tRF-003634 can alleviate podocyte injury by reducing the stability of TLR4 mRNA, possibly by competing with TLR4 mRNA to bind to YTH domain-containing protein 1 (YTHDC1). In conclusion, tRF-003634 was underexpressed in Adr-induced podocyte injury, and its overexpression alleviated podocyte injury in vitro and in vivo by reducing the stability of TLR4 mRNA. Public Library of Science 2023-10-19 /pmc/articles/PMC10586663/ /pubmed/37856510 http://dx.doi.org/10.1371/journal.pone.0293043 Text en © 2023 Gao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gao, Xiaoqing Qiao, Yunyang Li, Shanwen Shi, Huimin Qu, Gaoting Ji, Jialing Gan, Weihua Zhang, Aiqing tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA |
title | tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA |
title_full | tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA |
title_fullStr | tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA |
title_full_unstemmed | tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA |
title_short | tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA |
title_sort | trf-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of tlr4 mrna |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10586663/ https://www.ncbi.nlm.nih.gov/pubmed/37856510 http://dx.doi.org/10.1371/journal.pone.0293043 |
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