Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is key to preventing the progression of DN. Mitofusin 2 (Mfn2) regulates mitochondrial morphology and signaling, and is involved in the pathogenesis of numerous diseases. Furthermore, Mfn2 is also closely associated with the development of diabetes, but its functional roles in the diabetic kidney remain unknown. This study investigated the effect of Mfn2 at an early stage of DN. Mfn2 was overexpressed by adenovirus-mediated gene transfer in streptozotocin-induced diabetic rats. Clinical parameters (proteinuria, albumin/creatinine ratio), pathological changes, ultra-microstructural changes in nephrons, expression of collagen IV and phosph-p38, ROS production, mitochondrial function, and apoptosis were evaluated and compared with diabetic rats expressing control levels of Mfn2. Endogenous Mfn2 expression decreased with time in DN. Compared to the blank transfection control group, overexpression of Mfn2 decreased kidney weight relative to body weight, reduced proteinuria and ACR, and improved pathological changes typical of the diabetic kidney, like enlargement of glomeruli, accumulation of ECM, and thickening of the basement membrane. In addition, Mfn2 overexpression inhibited activation of p38, and the accumulation of ROS; prevented mitochondrial dysfunction; and reduced the synthesis of collagen IV, but did not affect apoptosis of kidney cells. This study demonstrates that Mfn2 overexpression can attenuate pathological changes in the kidneys of diabetic rats. Further studies are needed to clarify the underlying mechanism of this protective function. Mfn2 might be a potential therapeutic target for the treatment of early stage DN.
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PMID:Early protective effect of mitofusion 2 overexpression in STZ-induced diabetic rat kidney. 2209 88

Diabetic erectile dysfunction (ED) is a common complication in diabetes mellitus, and the efficacy of first-line therapies is not satisfactory. Recent studies revealed that corporal apoptosis was responsible for the nonresponsiveness of severe ED to phosphodiesterase type 5 inhibitors. Mitofusin 2 (Mfn2) is a versatile protein, regulating mitochondrial morphology and playing an important role in apoptosis. Several studies showed that expression of Mfn2 was decreased in STZ-induced diabetic rats' kidney, myocardium and retina, which was associated with diabetic nephropathy, cardiomyopathy and retinopathy respectively. In this study, our aim was to explore the expression of Mfn2 and apoptosis in diabetic rats' penes. We found that erectile function (ICP/MAP) elicited by electrical stimulation of cavernous nerve was markedly impaired in diabetic rats compared with the normal rats. The mRNA and protein levels of Mfn2 were found to be significantly reduced in diabetic rats' penile tissues. Compared with normal rats, the content of smooth muscle and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were dramatically decreased, and penile apoptotic index and expression of activated-caspase-3 were dramatically increased in diabetic rats. This data indicated that repression of Mfn2 in diabetic rats' penes might be associated with excessive apoptosis in diabetes-induced severe ED.
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PMID:Altered expression of mitofusin 2 in penile tissues of diabetic rats. 2368 52