MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway
The role of microRNAs in regulating tubulointerstitial fibrosis, a key feature of progressive chronic kidney disease, is of significant importance. LIN28A has been reported to attenuate renal fibrosis in obstructive nephropathy. Here, our objective was to investigate the precise biological function...
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Wolters Kluwer Medknow Publications
2024-08-01
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| Series: | Journal of Physiological Investigation |
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| Online Access: | https://journals.lww.com/10.4103/ejpi.EJPI-D-24-00019 |
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| author | Mingzhi Xu Mingjiao Pang Chunli Wang Na An Ruman Chen Yafei Bai Jiqing He Chunli Wang Yonghui Qi# |
| author_facet | Mingzhi Xu Mingjiao Pang Chunli Wang Na An Ruman Chen Yafei Bai Jiqing He Chunli Wang Yonghui Qi# |
| author_sort | Mingzhi Xu |
| collection | DOAJ |
| description | The role of microRNAs in regulating tubulointerstitial fibrosis, a key feature of progressive chronic kidney disease, is of significant importance. LIN28A has been reported to attenuate renal fibrosis in obstructive nephropathy. Here, our objective was to investigate the precise biological function of the miR-92a-3p/LIN28A axis in tubulointerstitial fibrosis. The human renal proximal tubular epithelial (HK-2) cell line was exposed to transforming growth factor (TGF)-β1, establishing an in vitro model mimicking tubulointerstitial fibrosis. Luciferase reporter assay was utilized to investigate the relationship between miR-92a-3p and LIN28A. Cell transfection techniques were employed to modify the expression of miR-92a-3p and LIN28A. An in vivo model of tubulointerstitial fibrosis was created by inducing unilateral ureteral obstruction (UUO) in C57BL/6N mice. Our initial observations showed that TGF-β1 treatment of HK-2 cells and the UUO mice model led to an increase in miR-92a-3p expression and a decrease in LIN28A expression. We confirmed that miR-92a-3p directly targeted LIN28A in HK-2 cells. In TGF-β1-stimulated HK-2 cells, knocking down miR-92a-3p notably reduced the levels of alpha smooth muscle actin and vimentin and concurrently enhanced the expression of E-cadherin. These changes were counteracted upon transfection with si-LIN28A. Thus, directing interventions toward miR-92a-3p holds the potential to emerge as a viable therapeutic approach for addressing tubulointerstitial fibrosis. |
| format | Article |
| id | doaj-art-1c10cdc30bcd40659cd88a243598e23d |
| institution | OA Journals |
| issn | 2950-6344 2950-6352 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Journal of Physiological Investigation |
| spelling | doaj-art-1c10cdc30bcd40659cd88a243598e23d2025-08-20T02:09:47ZengWolters Kluwer Medknow PublicationsJournal of Physiological Investigation2950-63442950-63522024-08-0167419820610.4103/ejpi.EJPI-D-24-00019MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT PathwayMingzhi XuMingjiao PangChunli WangNa AnRuman ChenYafei BaiJiqing HeChunli WangYonghui Qi#The role of microRNAs in regulating tubulointerstitial fibrosis, a key feature of progressive chronic kidney disease, is of significant importance. LIN28A has been reported to attenuate renal fibrosis in obstructive nephropathy. Here, our objective was to investigate the precise biological function of the miR-92a-3p/LIN28A axis in tubulointerstitial fibrosis. The human renal proximal tubular epithelial (HK-2) cell line was exposed to transforming growth factor (TGF)-β1, establishing an in vitro model mimicking tubulointerstitial fibrosis. Luciferase reporter assay was utilized to investigate the relationship between miR-92a-3p and LIN28A. Cell transfection techniques were employed to modify the expression of miR-92a-3p and LIN28A. An in vivo model of tubulointerstitial fibrosis was created by inducing unilateral ureteral obstruction (UUO) in C57BL/6N mice. Our initial observations showed that TGF-β1 treatment of HK-2 cells and the UUO mice model led to an increase in miR-92a-3p expression and a decrease in LIN28A expression. We confirmed that miR-92a-3p directly targeted LIN28A in HK-2 cells. In TGF-β1-stimulated HK-2 cells, knocking down miR-92a-3p notably reduced the levels of alpha smooth muscle actin and vimentin and concurrently enhanced the expression of E-cadherin. These changes were counteracted upon transfection with si-LIN28A. Thus, directing interventions toward miR-92a-3p holds the potential to emerge as a viable therapeutic approach for addressing tubulointerstitial fibrosis.https://journals.lww.com/10.4103/ejpi.EJPI-D-24-00019chronic kidney diseaselin28amir-92a-3ptubulointerstitial fibrosis |
| spellingShingle | Mingzhi Xu Mingjiao Pang Chunli Wang Na An Ruman Chen Yafei Bai Jiqing He Chunli Wang Yonghui Qi# MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway Journal of Physiological Investigation chronic kidney disease lin28a mir-92a-3p tubulointerstitial fibrosis |
| title | MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway |
| title_full | MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway |
| title_fullStr | MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway |
| title_full_unstemmed | MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway |
| title_short | MiR-92a-3p Knockdown Attenuates Transforming Growth Factor-β1-induced Tubulointerstitial Fibrosis by Targeting LIN28A-mediated EMT Pathway |
| title_sort | mir 92a 3p knockdown attenuates transforming growth factor β1 induced tubulointerstitial fibrosis by targeting lin28a mediated emt pathway |
| topic | chronic kidney disease lin28a mir-92a-3p tubulointerstitial fibrosis |
| url | https://journals.lww.com/10.4103/ejpi.EJPI-D-24-00019 |
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