Therapeutic Effect of Alprostadil in Diabetic Nephropathy: Possible Roles of Angiopoietin-2 and IL-18

Chen, Luo; Li, Ting; Zhang, Chun; Chen, Qing; Li, Zhenqiong; Liu, Jianshe; Wang, Yumei

doi:10.1159/000366309

Cited by 28 publications

(32 citation statements)

References 28 publications

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“…Previous studies have demonstrated that Morus alba exhibits comprehensive pharmacological effects that include, for example, hypoglycemic, immunomodulatory and antioxidant activities [19][20][21]. Our previous studies have found that RMP exerts hypoglycemic effect via regulating the intrapancreatic JNK/p38 pathway and blocking the IL-1/NF-κB pathway to protect against streptozotocin-induced apoptosis in pancreatic tissue and cytotoxicity in renal tissue [22][23][24]. Thus, we hypothesized that RMP might exert a beneficial effect on the development of DN.…”

Section: Mechanisms Of Protective Effect Of Ramulus Mori Polysaccharimentioning

confidence: 99%

Mechanisms of Protective Effect of Ramulus Mori Polysaccharides on Renal Injury in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Gao

et al. 2015

Cell Physiol Biochem

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Background: Diabetic nephropathy (DN) is the most important complication of diabetes and the most common cause of end-stage renal disease (ESRD). Aims: A recent study established that the Ramulus mori polysaccharides (RMP) exert antioxidant effects on DN in rats. Methods: The diabetic rats which induced by high-fat diet and streptozotocin injection were orally administered RMP by doses of 250, 500 and 1000 mg/kg daily for 8 weeks. The effects of RMP on hyperglycemia and other biochemical changes were examined in the sera and kidney tissues. Additionally, the pathological and ultrastructural changes and expressions of nuclear-factor kappa B (NF-κB) and transforming growth factor-ß1 (TGF-ß1) were assessed. Results: The results revealed that the serum levels of blood glucose, total cholesterol (TC) and triglycerides (TG) were significantly decreased by RMP. Furthermore, the blood urea nitrogen (BUN), serum creatinine (SCr) and 24-hour urine protein levels in the RMP-medicated rats were lower than those in untreated diabetic rats. Moreover, treatment of the DN rats with RMP normalized all biochemical changes, including the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum and kidney tissues. In contrast, the protein expression levels of NF-κB and TGF-ß1, which were enhanced in the kidneys of DN rats, were reduced by RMP. Conclusion: These results suggest that RMP improving the renal function of diabeitc rats possibly via its ameliorating antioxidant activities.

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Section: Mechanisms Of Protective Effect Of Ramulus Mori Polysaccharimentioning

confidence: 99%

Mechanisms of Protective Effect of Ramulus Mori Polysaccharides on Renal Injury in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Gao

et al. 2015

Cell Physiol Biochem

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“…Ang-2 is stored in endothelial cell Weibel-Palade bodies, and high concentrations of Ang-2 produce marked impairment of endothelial function. Ang-2 is known to increase levels of proinflammatory cytokines 32 . In the present study, serum IL-19 levels were positively correlated with Ang-2, and also a positive correlation between IL-19 and HbA1c, HOMA-IR was observed, which shows that IL-19 was closely associated with glucose metabolism disorders and vascular lesions in patients with type 2 diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

Association between interleukin‐19 and angiopoietin‐2 with vascular complications in type 2 diabetes

Li¹,

Yu²,

Juan-Yu

et al. 2016

J of Diabetes Invest

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Aims/IntroductionThe aim of the present study was to investigate the role of interleukin‐19 (IL‐19) in angiogenesis of type 2 diabetes mellitus with complications, and to assess the relationship of serum IL‐19 and angiopoietin‐2 (Ang‐2) in type 2 diabetes mellitus.Materials and MethodsThe group studied comprised of 240 patients with type 2 diabetes mellitus (132 men and 108 women), and included macrovascular complications, microvascular complications and type 2 diabetes mellitus without vascular complications. The control group consisted of 50 healthy blood donors. All participants were evaluated for: IL‐19, Ang‐2, fasting plasma glucose, fasting insulin and glycosylated hemoglobin.ResultsThe serum IL‐19 levels of type 2 diabetes mellitus patients with angiopathy were found to be significantly higher compared with patients without angiopathy. IL‐19 levels were significantly positively correlated with Ang‐2, homeostasis model assessment for insulin resistance and glycosylated hemoglobin (r = 0.769, 0.523 and 0.491, respectively, P < 0.01). In multivariable logistic regression analysis, IL‐19 levels (P = 0.01) were found to be independently associated with patients with type 2 diabetes mellitus complications.ConclusionsThese data are the first to implicate the association between the IL‐19 and type 2 diabetes mellitus with vascular complications. IL‐19 is significantly positively correlated with Ang‐2. The potential role of IL‐19 and Ang‐2 in the pathogenesis of vascular complications in type 2 diabetes could warrant further study.

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“…Murine glomerular endothelial cells (GEnCs) were purchased from Cell Biologics Company (C57-6014G) and were cultured according to the manufacturer's protocol and previously reports [16]. Cells were grown in Dulbecco's modified Eagle's medium (DMEM) (Gibco Invitrogen, LifeTechnologies, Scotland, UK) supplemented with 10% fetal bovine serum (FBS, Gibco Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Attenuation of Glomerular Endothelial Cells from High Glucose-Induced Injury by Blockade of MAD2B

Wang

Yu²,

Meng

et al. 2015

Cell Physiol Biochem

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Background/Aims: To assess the role of mitotic arrest-deficient 2-like protein 2 (MAD2B) in high glucose-induced injury in mouse glomerular endothelial cells (GEnCs). Methods: GEnCs were cultured in vitro, and MAD2B protein levels were measured by Western blot in cells stimulated with high glucose (30 mM) for various periods of time. MAD2B and scrambled shRNA were introduced into GEnCs by liposomal transfection. Cell proliferation, apoptosis, nitric oxide (NO) production, and monolayer permeability were then measured in cells grown in the following conditions: control, high glucose treatment, MAD2B shRNA transfection with high glucose treatment, and scrambled shRNA transfection with high glucose treatment. Results:High glucose increased the protein levels of MAD2B in GEnCs. Compared with control cells, apoptosis was increased by high glucose treatment, which was attenuated by transfection with MAD2B shRNA transfection. Cells treated with high glucose produced less NO than control cells, whereas MAD2B shRNA transfection increased NO production. Cell monolayer permeability was enhanced in high glucose treated cells, but MAD2B shRNA transfection reduced permeability. Conclusion: High glucose levels induced the expression of MAD2B in GEnCs, whereas suppressing its expression reduced high glucose-induced endothelial cell apoptosis and high permeability, and promoted cell proliferation and NO production.

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Therapeutic Effect of Alprostadil in Diabetic Nephropathy: Possible Roles of Angiopoietin-2 and IL-18

Cited by 28 publications

References 28 publications

Mechanisms of Protective Effect of Ramulus Mori Polysaccharides on Renal Injury in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Mechanisms of Protective Effect of Ramulus Mori Polysaccharides on Renal Injury in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Association between interleukin‐19 and angiopoietin‐2 with vascular complications in type 2 diabetes

Attenuation of Glomerular Endothelial Cells from High Glucose-Induced Injury by Blockade of MAD2B

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