DNA-PKcs participates in the repair of renal tubular epithelial cell injury
Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) and plays a central role in mediating cell damage and ultimately acute tubular necrosis. Renal proximal tubular epithelial cells (PTECs) possess intrinsic repair mechanisms, yet the molecular pathways underpinning their...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2537811 |
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| author | Dan Feng Yu-Jie Hu Lei Sun Jing Zhang Xiao-Ling Niu Wen-Yan Huang |
| author_facet | Dan Feng Yu-Jie Hu Lei Sun Jing Zhang Xiao-Ling Niu Wen-Yan Huang |
| author_sort | Dan Feng |
| collection | DOAJ |
| description | Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) and plays a central role in mediating cell damage and ultimately acute tubular necrosis. Renal proximal tubular epithelial cells (PTECs) possess intrinsic repair mechanisms, yet the molecular pathways underpinning their ability to recover after I/R injury remain incompletely understood. DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine/threonine kinase, is pivotal in DNA damage repair, genomic stability, cell cycle regulation, and mitochondrial dysfunction. Given its central roles in maintaining cellular homeostasis, we hypothesized that DNA-PKcs is critically involved in orchestrating the intrinsic repair mechanisms of renal tubular epithelial cells following I/R injury. In this study, we investigate the involvement of DNA-PKcs in the repair of tubular epithelial cell damage induced by renal I/R injury. Using both in vitro and in vivo models, we demonstrate that DNA-PKcs expression is significantly upregulated during the acute phase of kidney injury and returns to baseline levels upon resolution of the damage. In the hypoxia/reoxygenation (H/R) model using NRK-52E cells, treatment with the DNA-PKcs inhibitor NU7441 resulted in mitochondrial swelling. Additionally, the expression levels of DNA damage and epithelial-mesenchymal transition markers such as γ-H2AX, α-SMA, and vimentin were notably prolonged. Moreover, DNA-PKcs inhibition significantly impaired cell proliferation, induced a G1/S phase arrest under normoxic conditions, and resulted in G2/M phase arrest following H/R. Our study provides that DNA-PKcs acts as a promising therapeutic target for mitigating AKI and promoting renal regeneration. |
| format | Article |
| id | doaj-art-9ec026d6684949389c187ec641ee48e1 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-9ec026d6684949389c187ec641ee48e12025-08-20T03:09:27ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2537811DNA-PKcs participates in the repair of renal tubular epithelial cell injuryDan Feng0Yu-Jie Hu1Lei Sun2Jing Zhang3Xiao-Ling Niu4Wen-Yan Huang5Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of medicine, Shanghai Jiao Tong University, Shanghai, ChinaIschemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) and plays a central role in mediating cell damage and ultimately acute tubular necrosis. Renal proximal tubular epithelial cells (PTECs) possess intrinsic repair mechanisms, yet the molecular pathways underpinning their ability to recover after I/R injury remain incompletely understood. DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine/threonine kinase, is pivotal in DNA damage repair, genomic stability, cell cycle regulation, and mitochondrial dysfunction. Given its central roles in maintaining cellular homeostasis, we hypothesized that DNA-PKcs is critically involved in orchestrating the intrinsic repair mechanisms of renal tubular epithelial cells following I/R injury. In this study, we investigate the involvement of DNA-PKcs in the repair of tubular epithelial cell damage induced by renal I/R injury. Using both in vitro and in vivo models, we demonstrate that DNA-PKcs expression is significantly upregulated during the acute phase of kidney injury and returns to baseline levels upon resolution of the damage. In the hypoxia/reoxygenation (H/R) model using NRK-52E cells, treatment with the DNA-PKcs inhibitor NU7441 resulted in mitochondrial swelling. Additionally, the expression levels of DNA damage and epithelial-mesenchymal transition markers such as γ-H2AX, α-SMA, and vimentin were notably prolonged. Moreover, DNA-PKcs inhibition significantly impaired cell proliferation, induced a G1/S phase arrest under normoxic conditions, and resulted in G2/M phase arrest following H/R. Our study provides that DNA-PKcs acts as a promising therapeutic target for mitigating AKI and promoting renal regeneration.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2537811DNA-PKcsDNA-PKcs inhibitorrenal tubular epithelial cell injuryrepair |
| spellingShingle | Dan Feng Yu-Jie Hu Lei Sun Jing Zhang Xiao-Ling Niu Wen-Yan Huang DNA-PKcs participates in the repair of renal tubular epithelial cell injury Renal Failure DNA-PKcs DNA-PKcs inhibitor renal tubular epithelial cell injury repair |
| title | DNA-PKcs participates in the repair of renal tubular epithelial cell injury |
| title_full | DNA-PKcs participates in the repair of renal tubular epithelial cell injury |
| title_fullStr | DNA-PKcs participates in the repair of renal tubular epithelial cell injury |
| title_full_unstemmed | DNA-PKcs participates in the repair of renal tubular epithelial cell injury |
| title_short | DNA-PKcs participates in the repair of renal tubular epithelial cell injury |
| title_sort | dna pkcs participates in the repair of renal tubular epithelial cell injury |
| topic | DNA-PKcs DNA-PKcs inhibitor renal tubular epithelial cell injury repair |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2537811 |
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