Mitochondria-Targeted Peptide SS31 Attenuates Renal Tubulointerstitial Injury via Inhibiting Mitochondrial Fission in Diabetic Mice
| العنوان: | Mitochondria-Targeted Peptide SS31 Attenuates Renal Tubulointerstitial Injury via Inhibiting Mitochondrial Fission in Diabetic Mice |
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| المؤلفون: | Ming Yang, Shikun Yang, Aimei Li, Yachun Han, Shiqi Tang, Wei Zhang, Lingfeng Zeng, Ming Zhan, Can-hui Peng, Pan-ai Song, Hao Zhang, Na Song |
| المصدر: | Oxidative Medicine and Cellular Longevity, Vol 2019 (2019) Oxidative Medicine and Cellular Longevity |
| بيانات النشر: | Hindawi Limited, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Mitochondrial ROS, Aging, medicine.medical_specialty, Article Subject, Mitochondrion, medicine.disease_cause, Mitochondrial Dynamics, Biochemistry, Diabetes Mellitus, Experimental, Diabetic nephropathy, Mice, Random Allocation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Animals, Humans, Diabetic Nephropathies, lcsh:QH573-671, Creatinine, lcsh:Cytology, Cell Biology, General Medicine, medicine.disease, Mitochondria, Mice, Inbred C57BL, Kidney Tubules, 030104 developmental biology, Endocrinology, chemistry, Apoptosis, 030220 oncology & carcinogenesis, Tubulointerstitial fibrosis, Nephritis, Interstitial, Mitochondrial fission, Reactive Oxygen Species, Oligopeptides, Oxidative stress, Research Article |
| الوصف: | Objective. Renal tubular injury is an early characteristic of diabetic nephropathy (DN) that is related to mitochondrial dysfunction. In this study, we explore the effects and mechanisms of mitochondria-targeted peptide SS31 on renal tubulointerstitial injury in DN. Method. 40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks. Renal lesions and the expression of Drp1, Mfn1, Bcl-2, Bax, Caspase1, IL-1β, and FN were detected. In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1. Mitochondrial ROS, membrane potential, and morphology have been detected to evaluate the mitochondrial function. Results. Compared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group. Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group. SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1β, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1. Additionally, mitochondria exhibit focal enlargement and crista swelling in renal tubular cells of diabetic mice, while SS31 treatment could partially block these changes. An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1β, and FN in HK-2 cells under high-glucose conditions. Conclusion. SS31 protected renal tubulointerstitial injury in diabetic mice through a decrease in mitochondrial fragmentation via suppressing the expression of Drp1 and increasing the expression of Mfn1. |
| وصف الملف: | text/xhtml |
| تدمد: | 1942-0994 1942-0900 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2c4c4323a840a7704c978ec18288047d https://doi.org/10.1155/2019/2346580 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2c4c4323a840a7704c978ec18288047d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19420994 19420900 |
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