Early protective effect of mitofusion 2 overexpression in STZ-induced diabetic rat kidney

Tang, Wanjie; Wu, Wei; Zeng, Xiao; Hong, Bo; Huang, Shu‐Ling

doi:10.1007/s12020-011-9555-1

Cited by 32 publications

(37 citation statements)

References 62 publications

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Section: Mitochondria and Renal Diseasessupporting

confidence: 64%

“…In line with this finding, kidney-specific overexpression of MFN2 protects rats from streptozotocin-induced diabetic nephropathy 193 . MFN2 overexpression decreased ROS production, decreased kidney volume and attenuated the pathological changes seen in the diabetic kidney 193 . Induced in high glucose 1 (IHG1; also known as THG1L) is another protein that is involved in mitochondrial fusion and has been shown to regulate mitochondrial dynamics and biogenesis in the diabetic kidney 194 .…”

Section: Mitochondria and Renal Diseasessupporting

confidence: 64%

“…Patients with diabetes mellitus have reduced levels of the fusion protein MFN2 193 . In line with this finding, kidney-specific overexpression of MFN2 protects rats from streptozotocin-induced diabetic nephropathy 193 .…”

Section: Mitochondria and Renal Diseasesmentioning

confidence: 99%

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Mitochondrial energetics in the kidney

2017

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The kidney requires a large number of mitochondria to remove waste from the blood and regulate fluid and electrolyte balance. Mitochondria provide the energy to drive these important functions and can adapt to different metabolic conditions through a number of signalling pathways (for example, mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) pathways) that activate the transcriptional co-activator peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α), and by balancing mitochondrial dynamics and energetics to maintain mitochondrial homeostasis. Mitochondrial dysfunction leads to a decrease in ATP production, alterations in cellular functions and structure, and the loss of renal function. Persistent mitochondrial dysfunction has a role in the early stages and progression of renal diseases, such as acute kidney injury (AKI) and diabetic nephropathy, as it disrupts mitochondrial homeostasis and thus normal kidney function. Improving mitochondrial homeostasis and function has the potential to restore renal function, and administering compounds that stimulate mitochondrial biogenesis can restore mitochondrial and renal function in mouse models of AKI and diabetes mellitus. Furthermore, inhibiting the fission protein dynamin 1-like protein (DRP1) might ameliorate ischaemic renal injury by blocking mitochondrial fission.

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Section: Mitochondria and Renal Diseasessupporting

confidence: 64%

Section: Mitochondria and Renal Diseasessupporting

confidence: 64%

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Mitochondrial energetics in the kidney

2017

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“…For example, excessive mitochondrial fission is essential for apoptosis (Thomas et al, 2012). Tang et al (2012) showed that mfn2 overexpression attenuated pathological changes in the kidneys of diabetic rats. Meanwhile, Wang et al (2012) showed that deletion of ROCK1 in diabetic mice prevented mitochondrial fission, whereas podocyte-specific cA-ROCK1 mice exhibited increased mitochondrial fission associated with less significant kidney damage, indicating that mitochondrial dysfunction plays an important role in diabetic nephropathy.…”

Section: Discussionmentioning

confidence: 99%

Zhi-Long-Huo-Xue-Tong-Yu modulates mitochondrial fission through the ROCK1 pathway in mitochondrial dysfunction caused by streptozotocin-induced diabetic kidney injury

Wu¹,

Zhang²,

Yang³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Zhi-Long-Huo-Xue-Tong-Yu (ZLHXTY) is a defined mixture of 5 herbs developed by Professor S.J. Yang according to the Buyang Huanwu decoction method, which has been recorded in the Yilingaicuo. This study investigated the renoprotective effects of ZLHXTY on mitochondrial dysfunction induced by diabetic kidney injury in a diabetic rat model. Diabetes was induced by a single intravenous injection of streptozotocin. Rats were daily fed either ZLHXTY or vehicle beginning in the 1st week after injection. Levels of mitofusin 2 (mfn2), dynamin-related protein 1 (Drp1), caspase-9, and rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) were detected using Western blotting. Levels of intracellular calcium and adenosine triphosphate (ATP) were examined using an enzyme-linked immunosorbent assay. An electron microscopic examination of kidney tissue was performed. The levels of mfn2 and ATP in the diabetes and ZLHXTY groups decreased from the 4th week after modeling. The expression levels of Drp1, ROCK1, and caspase-9 increased in the diabetes group but decreased in the ZLHXTY group from the 4th week after modeling. Compared with the diabetes group, ZLHXTY treatment decreased the mesangial expansion index and proteinuria levels, and improved the pathological changes typical of diabetic kidney injury. Furthermore, ZLHXTY treatment inhibited the activation of ROCK1 and expression of Drp1 and caspase-9, but did not affect the expression of mfn2. This study indicates that ZLHXTY treatment could protect kidney tissue from diabetic injury through the ROCK1 pathway response to mitochondrial dysfunction induced by diabetes.

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“…Following this (after 3 days), blood glucose levels was detected utilizing One-Touch strip. Rats with blood glucose concentrations above 13.9 mmol/L were considered as diabetic and were used following experiments [5, 20]. A week later, diabetic rats were randomly administered fenugreek (9 g seed powder/kg, DF group, n = 10) daily for 12 weeks or treated with vehicle control (DN group, n = 10), respectively.…”

Section: Methodsmentioning

confidence: 99%

Fenugreek Prevents the Development of STZ‐Induced Diabetic Nephropathy in a Rat Model of Diabetes

Jin

Shi

Zou

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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The present study aims to examine the protective effect of fenugreek and the underlying mechanism against the development of diabetic nephropathy (DN) in streptozotocin- (STZ-) induced diabetic rats. A rat model of diabetes was successfully established by direct injection of STZ and then the rats were administered an interventional treatment of fenugreek. Parameters of renal function, including blood glucose, albuminuria, hemoglobin A1c (HbA1c), dimethyl formamide (DMF), blood urine nitrogen (BUN), serum creatinine (Scr), and kidney index (KI), were detected in the three groups (Con, DN, and DF). Oxidative stress was determined by the activity of antioxidase. Extracellular matrix (ECM) accumulation and other morphological alterations were evaluated by means of immunohistochemistry and electron microscope. Quantitive (q)PCR was employed to detect the mRNA expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) and protein expression was determined with western blot analysis. DN rats in the present study demonstrated a significant renal dysfunction, ECM accumulation, pathological alteration, and oxidative stress, while the symptoms were evidently reduced by fenugreek treatment. Furthermore, the upregulation of TGF-β1 and CTGF at a transcriptional and translational level in DN rats was distinctly inhibited by fenugreek. Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat model.

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Early protective effect of mitofusion 2 overexpression in STZ-induced diabetic rat kidney

Cited by 32 publications

References 62 publications

Mitochondrial energetics in the kidney

Mitochondrial energetics in the kidney

Zhi-Long-Huo-Xue-Tong-Yu modulates mitochondrial fission through the ROCK1 pathway in mitochondrial dysfunction caused by streptozotocin-induced diabetic kidney injury

Fenugreek Prevents the Development of STZ‐Induced Diabetic Nephropathy in a Rat Model of Diabetes

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