CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis
Renal fibrosis is a long-term and progressively worsening condition that impacts kidney function during aging and in the context of chronic kidney disease (CKD). CKD and renal fibrosis affect approximately 10% of the global population and are prevalent in about half of individuals over the age of 70...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Renal Failure |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2396455 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849763380636680192 |
|---|---|
| author | Qian Huang Kaiyi Zhong Jiali Wei |
| author_facet | Qian Huang Kaiyi Zhong Jiali Wei |
| author_sort | Qian Huang |
| collection | DOAJ |
| description | Renal fibrosis is a long-term and progressively worsening condition that impacts kidney function during aging and in the context of chronic kidney disease (CKD). CKD and renal fibrosis affect approximately 10% of the global population and are prevalent in about half of individuals over the age of 70. Despite ongoing research, the mechanisms underlying renal fibrosis are still not well understood, and there is currently a lack of effective treatments available. In the present study, we demonstrated a significant increase of circPWWP2A in renal tubular cells both in vivo and in vitro models of renal fibrosis. Suppressing circPWWP2A has the potential to reduce mitochondrial dysfunction and the production of mitochondrial reactive oxygen species (mtROS), ultimately leading to the inhibition of renal fibrosis. Whereas, supplementation of circPWWP2A led to more serve mitochondrial dysfunction, mtROS production and renal fibrosis. Mechanistically, we found the expression of circPWWP2A was negatively correlated with the expression of miR-182. And we further confirmed miR-182 was the direct target of circPWWP2A by dual-luciferase reporter assay and RIP assay. Then, we found miR-182 suppressed the expression of ROCK1 in both in vitro and in vivo models of renal fibrosis. Luciferase microRNA target reporter assay further indicated ROCK1 as a direct target of miR-182. Knockdown of ROCK1 inhibits renal fibrosis and mitochondrial dysfunction, suggesting ROCK1 not only served as an injurious role in mitochondrial homeostasis but also a pro-fibrotic factor in CKD. Taking together, our findings suggest that circPWWP2A may promote renal interstitial fibrosis by modulating miR-182/ROCK1-mediated mitochondrial dysfunction. |
| format | Article |
| id | doaj-art-0b1e726242d64b9a8b2dfd5f4710d89b |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-0b1e726242d64b9a8b2dfd5f4710d89b2025-08-20T03:05:25ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2396455CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axisQian Huang0Kaiyi Zhong1Jiali Wei2Department of Nephrology, Haikou Third People’s Hospital, Haikou, Hainan, ChinaDepartment of Nephrology, Danzhou West Central Hospital, Danzhou, Hainan, ChinaDepartment of Nephrology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical College), Haikou, ChinaRenal fibrosis is a long-term and progressively worsening condition that impacts kidney function during aging and in the context of chronic kidney disease (CKD). CKD and renal fibrosis affect approximately 10% of the global population and are prevalent in about half of individuals over the age of 70. Despite ongoing research, the mechanisms underlying renal fibrosis are still not well understood, and there is currently a lack of effective treatments available. In the present study, we demonstrated a significant increase of circPWWP2A in renal tubular cells both in vivo and in vitro models of renal fibrosis. Suppressing circPWWP2A has the potential to reduce mitochondrial dysfunction and the production of mitochondrial reactive oxygen species (mtROS), ultimately leading to the inhibition of renal fibrosis. Whereas, supplementation of circPWWP2A led to more serve mitochondrial dysfunction, mtROS production and renal fibrosis. Mechanistically, we found the expression of circPWWP2A was negatively correlated with the expression of miR-182. And we further confirmed miR-182 was the direct target of circPWWP2A by dual-luciferase reporter assay and RIP assay. Then, we found miR-182 suppressed the expression of ROCK1 in both in vitro and in vivo models of renal fibrosis. Luciferase microRNA target reporter assay further indicated ROCK1 as a direct target of miR-182. Knockdown of ROCK1 inhibits renal fibrosis and mitochondrial dysfunction, suggesting ROCK1 not only served as an injurious role in mitochondrial homeostasis but also a pro-fibrotic factor in CKD. Taking together, our findings suggest that circPWWP2A may promote renal interstitial fibrosis by modulating miR-182/ROCK1-mediated mitochondrial dysfunction.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2396455Renal fibrosisCircPWWP2AmiR-182ROCK1mitochondrial dysfunction |
| spellingShingle | Qian Huang Kaiyi Zhong Jiali Wei CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis Renal Failure Renal fibrosis CircPWWP2A miR-182 ROCK1 mitochondrial dysfunction |
| title | CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis |
| title_full | CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis |
| title_fullStr | CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis |
| title_full_unstemmed | CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis |
| title_short | CircPWWP2A promotes renal interstitial fibrosis through modulating miR-182/ROCK1 axis |
| title_sort | circpwwp2a promotes renal interstitial fibrosis through modulating mir 182 rock1 axis |
| topic | Renal fibrosis CircPWWP2A miR-182 ROCK1 mitochondrial dysfunction |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2396455 |
| work_keys_str_mv | AT qianhuang circpwwp2apromotesrenalinterstitialfibrosisthroughmodulatingmir182rock1axis AT kaiyizhong circpwwp2apromotesrenalinterstitialfibrosisthroughmodulatingmir182rock1axis AT jialiwei circpwwp2apromotesrenalinterstitialfibrosisthroughmodulatingmir182rock1axis |