Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy
This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonis...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2347446 |
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| author | Zebo Hu Qianwen Zhu Ying Wang Xue Deng Hui Yang Mingjun Zhou Jiyuan Zhang Hao Wang Haosen Wang Lin Wang Cui Zhang Shu Li |
| author_facet | Zebo Hu Qianwen Zhu Ying Wang Xue Deng Hui Yang Mingjun Zhou Jiyuan Zhang Hao Wang Haosen Wang Lin Wang Cui Zhang Shu Li |
| author_sort | Zebo Hu |
| collection | DOAJ |
| description | This study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro, CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells. Furthermore, results obtained in vivo showed that HIF-1α protein expression in the renal tubules of diabetic rats was significantly downregulated by YC-1 treatment. Meanwhile, lipid accumulation in the tubules of the DM + YC-1 group was markedly decreased in comparison to the DM + DMSO group. Accordingly, PAS staining revealed that the pathological injury caused to the tubular epithelial cells was alleviated by YC-1 treatment. Furthermore, the blood glucose level, urine albumin creatinine ratio, and NAG creatinine ratio in the DM + YC-1 group were significantly decreased compared to the DM + DMSO group. Moreover, the protein expression levels of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in diabetic kidneys were decreased by YC-1 treatment. Our findings demonstrate that the activation of HIF-1α contributed to interstitial injury in a rat model of diabetic nephropathy and that the underlying mechanism involved the induction of lipid accumulation. |
| format | Article |
| id | doaj-art-b583a48532c8479c9d7c0e83398e7317 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-b583a48532c8479c9d7c0e83398e73172025-01-23T04:17:47ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2347446Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathyZebo Hu0Qianwen Zhu1Ying Wang2Xue Deng3Hui Yang4Mingjun Zhou5Jiyuan Zhang6Hao Wang7Haosen Wang8Lin Wang9Cui Zhang10Shu Li11Department of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaDepartment of Pathophysiology, School of Basic Medicine, Wannan Medical College, Wuhu, ChinaThis study is intended to explore the effect of hypoxia-inducible factor-1α (HIF-1α) activation on lipid accumulation in the diabetic kidney. A type 1 diabetic rat model was established by STZ intraperitoneal injection. Cobalt chloride (CoCl2) and YC-1 were used as the HIF-1α activator and antagonist, respectively. CoCl2 treatment significantly increased HIF-1α expression, accelerated lipid deposition, and accelerated tubular injury in diabetic kidneys. In vitro, CoCl2 effectively stabilized HIF-1α and increased its transportation from the cytoplasm to the nucleus, which was accompanied by significantly increased lipid accumulation in HK-2 cells. Furthermore, results obtained in vivo showed that HIF-1α protein expression in the renal tubules of diabetic rats was significantly downregulated by YC-1 treatment. Meanwhile, lipid accumulation in the tubules of the DM + YC-1 group was markedly decreased in comparison to the DM + DMSO group. Accordingly, PAS staining revealed that the pathological injury caused to the tubular epithelial cells was alleviated by YC-1 treatment. Furthermore, the blood glucose level, urine albumin creatinine ratio, and NAG creatinine ratio in the DM + YC-1 group were significantly decreased compared to the DM + DMSO group. Moreover, the protein expression levels of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in diabetic kidneys were decreased by YC-1 treatment. Our findings demonstrate that the activation of HIF-1α contributed to interstitial injury in a rat model of diabetic nephropathy and that the underlying mechanism involved the induction of lipid accumulation.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2347446Diabetic nephropathyHIF-1αYC-1lipid accumulationtubulesHK-2 |
| spellingShingle | Zebo Hu Qianwen Zhu Ying Wang Xue Deng Hui Yang Mingjun Zhou Jiyuan Zhang Hao Wang Haosen Wang Lin Wang Cui Zhang Shu Li Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy Renal Failure Diabetic nephropathy HIF-1α YC-1 lipid accumulation tubules HK-2 |
| title | Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy |
| title_full | Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy |
| title_fullStr | Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy |
| title_full_unstemmed | Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy |
| title_short | Lipid nephrotoxicity mediated by HIF-1α activation accelerates tubular injury in diabetic nephropathy |
| title_sort | lipid nephrotoxicity mediated by hif 1α activation accelerates tubular injury in diabetic nephropathy |
| topic | Diabetic nephropathy HIF-1α YC-1 lipid accumulation tubules HK-2 |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2347446 |
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