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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293043&type=printable |
| _version_ | 1797649629911711744 |
|---|---|
| author | Xiaoqing Gao Yunyang Qiao Shanwen Li Huimin Shi Gaoting Qu Jialing Ji Weihua Gan Aiqing Zhang |
| author_facet | Xiaoqing Gao Yunyang Qiao Shanwen Li Huimin Shi Gaoting Qu Jialing Ji Weihua Gan Aiqing Zhang |
| author_sort | Xiaoqing Gao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T15:49:02Z |
| format | Article |
| id | doaj.art-7b688539ce8d4bc6953ef6180f5c39e9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T15:49:02Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7b688539ce8d4bc6953ef6180f5c39e92023-10-26T05:31:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011810e029304310.1371/journal.pone.0293043tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA.Xiaoqing GaoYunyang QiaoShanwen LiHuimin ShiGaoting QuJialing JiWeihua GanAiqing ZhangPodocyte 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293043&type=printable |
| spellingShingle | Xiaoqing Gao Yunyang Qiao Shanwen Li Huimin Shi Gaoting Qu Jialing Ji Weihua Gan Aiqing Zhang tRF-003634 alleviates adriamycin-induced podocyte injury by reducing the stability of TLR4 mRNA. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0293043&type=printable |
| work_keys_str_mv | AT xiaoqinggao trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT yunyangqiao trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT shanwenli trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT huiminshi trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT gaotingqu trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT jialingji trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT weihuagan trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna AT aiqingzhang trf003634alleviatesadriamycininducedpodocyteinjurybyreducingthestabilityoftlr4mrna |