Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis
Objective To investigate the role and underlying mechanisms of oxoglutarate dehydrogenase-L (OGDHL) in renal fibrosis. Methods Twelve male wild-type C57BL/6J mice (8 weeks old, weighting about 25 g) were randomly divided into control group and model group (n=6). A mouse model of renal fibrosis...
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Editorial Office of Journal of Army Medical University
2025-06-01
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| author | YANG Yingxian HUANG Yinghui ZHAO Jinghong |
| author_facet | YANG Yingxian HUANG Yinghui ZHAO Jinghong |
| author_sort | YANG Yingxian |
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| description | Objective To investigate the role and underlying mechanisms of oxoglutarate dehydrogenase-L (OGDHL) in renal fibrosis. Methods Twelve male wild-type C57BL/6J mice (8 weeks old, weighting about 25 g) were randomly divided into control group and model group (n=6). A mouse model of renal fibrosis was established by unilateral ureteral obstruction (UUO). HE staining, immunofluorescence assay, and immunohistochemical and Masson staining were applied to assess the extent of renal fibrosis. Human kidney-2 proximal tubule cell line (HK-2) were randomly divided into blank plasmid group (Vector), OGDHL overexpression group (OGDHL OE), blank plasmid + TGF-β1 treatment group (TGF-β1+Vector), TGF-β1 treatment and OGDHL overexpression group (TGF-β1+OGDHL OE). Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology. RT-qPCR, Western blotting and immunofluorescence assay were used to detect the expression levels of OGDHL and mitochondrial metabolism-related genes. Adenosine triphosphate (ATP) level, oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and other mitochondrial metabolism-related indicators were detected with corresponding reagent kits and Agilent Seahorse. Results UUO operation resulted in obvious thinning of the renal cortex, significant hydronephrosis. HE staining revealed that tubular atrophy accompanied by dilated tubular lumens in the kidneys. Immunofluorescence, immunohistochemical and Masson staining showed obvious renal fibrosis after UUO operation. In the mouse model of renal fibrosis, the expression of OGDHL was decreased by 82.9% at mRNA level (P<0.001) and 81.9% at protein level (P<0.001), the production of mitochondrial ATP was reduced by 0.970±0.151 µmol/L (P<0.01), and notable damaged mitochondrial structure was observed, with maximum breathing capacity decreased by 25.260±1.920 pmol/min (P<0.001), expression levels of fatty acid oxidation-related genes were declined by 50.2% (P<0.05), while glycolysis was enhanced, with the genes related to glycolysis increased by 2.5 times when compared with those in the control group (P<0.05). After OGDHL overexpression, mitochondrial morphological damage was significantly improved, ATP production was increased by 0.980±0.090 µmol/L (P<0.05), with significantly alleviated energy metabolism disorder and renal fibrosis (P<0.05). Conclusion OGDHL regulates mitochondrial metabolic reprogramming of renal tubular epithelial cells to alleviate fibrosis, suggesting that OGDHL may be a new therapeutic target for renal fibrosis.
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| format | Article |
| id | doaj-art-c8cb133baef44847a2cd8ed1fbfbf16c |
| institution | OA Journals |
| issn | 2097-0927 |
| language | zho |
| publishDate | 2025-06-01 |
| publisher | Editorial Office of Journal of Army Medical University |
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| series | 陆军军医大学学报 |
| spelling | doaj-art-c8cb133baef44847a2cd8ed1fbfbf16c2025-08-20T02:22:45ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272025-06-0147111145115410.16016/j.2097-0927.202501053Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosisYANG Yingxian0HUANG Yinghui1ZHAO Jinghong2Department of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Diseases， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， ChinaDepartment of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Diseases， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， ChinaDepartment of Nephrology， Chongqing Key Laboratory for Prevention and Treatment of Kidney Diseases， Chongqing Clinical Research Center of Kidney and Urology Diseases， Second Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， China Objective To investigate the role and underlying mechanisms of oxoglutarate dehydrogenase-L (OGDHL) in renal fibrosis. Methods Twelve male wild-type C57BL/6J mice (8 weeks old, weighting about 25 g) were randomly divided into control group and model group (n=6). A mouse model of renal fibrosis was established by unilateral ureteral obstruction (UUO). HE staining, immunofluorescence assay, and immunohistochemical and Masson staining were applied to assess the extent of renal fibrosis. Human kidney-2 proximal tubule cell line (HK-2) were randomly divided into blank plasmid group (Vector), OGDHL overexpression group (OGDHL OE), blank plasmid + TGF-β1 treatment group (TGF-β1+Vector), TGF-β1 treatment and OGDHL overexpression group (TGF-β1+OGDHL OE). Transmission electron microscopy (TEM) was employed to observe mitochondrial morphology. RT-qPCR, Western blotting and immunofluorescence assay were used to detect the expression levels of OGDHL and mitochondrial metabolism-related genes. Adenosine triphosphate (ATP) level, oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and other mitochondrial metabolism-related indicators were detected with corresponding reagent kits and Agilent Seahorse. Results UUO operation resulted in obvious thinning of the renal cortex, significant hydronephrosis. HE staining revealed that tubular atrophy accompanied by dilated tubular lumens in the kidneys. Immunofluorescence, immunohistochemical and Masson staining showed obvious renal fibrosis after UUO operation. In the mouse model of renal fibrosis, the expression of OGDHL was decreased by 82.9% at mRNA level (P<0.001) and 81.9% at protein level (P<0.001), the production of mitochondrial ATP was reduced by 0.970±0.151 µmol/L (P<0.01), and notable damaged mitochondrial structure was observed, with maximum breathing capacity decreased by 25.260±1.920 pmol/min (P<0.001), expression levels of fatty acid oxidation-related genes were declined by 50.2% (P<0.05), while glycolysis was enhanced, with the genes related to glycolysis increased by 2.5 times when compared with those in the control group (P<0.05). After OGDHL overexpression, mitochondrial morphological damage was significantly improved, ATP production was increased by 0.980±0.090 µmol/L (P<0.05), with significantly alleviated energy metabolism disorder and renal fibrosis (P<0.05). Conclusion OGDHL regulates mitochondrial metabolic reprogramming of renal tubular epithelial cells to alleviate fibrosis, suggesting that OGDHL may be a new therapeutic target for renal fibrosis. https://aammt.tmmu.edu.cn/html/202501053.htmlrenal fibrosisoxoglutarate dehydrogenase-lmitochondrial metabolism reprogrammingrenal tubular epithelial cells |
| spellingShingle | YANG Yingxian HUANG Yinghui ZHAO Jinghong Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis 陆军军医大学学报 renal fibrosis oxoglutarate dehydrogenase-l mitochondrial metabolism reprogramming renal tubular epithelial cells |
| title | Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis |
| title_full | Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis |
| title_fullStr | Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis |
| title_full_unstemmed | Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis |
| title_short | Oxoglutarate dehydrogenase-L regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis |
| title_sort | oxoglutarate dehydrogenase l regulates mitochondrial metabolism reprogramming of renal tubular epithelial cells to alleviate renal fibrosis |
| topic | renal fibrosis oxoglutarate dehydrogenase-l mitochondrial metabolism reprogramming renal tubular epithelial cells |
| url | https://aammt.tmmu.edu.cn/html/202501053.html |
| work_keys_str_mv | AT yangyingxian oxoglutaratedehydrogenaselregulatesmitochondrialmetabolismreprogrammingofrenaltubularepithelialcellstoalleviaterenalfibrosis AT huangyinghui oxoglutaratedehydrogenaselregulatesmitochondrialmetabolismreprogrammingofrenaltubularepithelialcellstoalleviaterenalfibrosis AT zhaojinghong oxoglutaratedehydrogenaselregulatesmitochondrialmetabolismreprogrammingofrenaltubularepithelialcellstoalleviaterenalfibrosis |