Targeting TGF could counter diabetic nephropathy

Greener, Mark

doi:10.1016/s1357-4310(00)01788-3

Cited by 5 publications

(3 citation statements)

References 1 publication

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“…TGF- β 1 has been identified as the regulator of ECM accumulation. In diabetic patients and animal models, progressively raised expression of mRNA and protein of TGF- β 1 was detected and always accompanied with the increased production of ECM components, whereas blockade of the overexpression of TGF- β 1 could prevent the pathological alterations, such as ECM accumulation and GBM thickening [ 38 – 41 ]. In the present study, the diabetic rats had an upregulation of TGF- β 1 in mRNA and protein expression ( Figure 4 ), which was consistent with the results of previous studies.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Further studies regarding the role of TGF-β in the pathogenesis of DN demonstrated that the overexpression of TGF-β in diabetic kidneys is responsible for the early pathological changes of DN, including the glomerular basement membrane thickening and mesangial matrix expansion [15,103,[112][113][114][115]. Blockade of TGF-β expression or function has been shown to reduce diabetic renal damage or prevent the occurrence of DN [19,116]. The exact mechanisms responsible for the up-regulation of TGF-β in diabetic kidney are still unclear.…”

Section: Tgf-βmentioning

confidence: 99%

“…In the early stages of DR and DN, angiogenic growth factors such as vascular endothelial growth factor (VEGF) and transforming growth factors-β (TGF-β) have been shown to be significantly up-regulated [13][14][15][16][17][18]. Blockade of VEGF or TGF-β has been shown to prevent the formation of DR and DN in diabetic animal models [19,20]. These findings suggest that angiogenic growth factors are crucial mediators in the pathogenesis of DR and DN.…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Angiogenic Inhibitors: A Potential Pathogenic Mechanism for Diabetic Complications

Xing

Zhang²,

Wang³

2005

CDR

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Diabetic retinopathy (DR) and diabetic nephropathy (DN) are the most common microvascular complications of diabetes. DR is a leading cause of blindness, and DN is a major cause of end-stage renal diseases. Diabetic macular edema (DME) resulting from increased vascular permeability in the retina and retinal neovascularization (NV) represent two major pathological changes in DR and are the primary causes of vision loss in diabetic patients. Previous studies have shown that angiogenic factors such as vascular endothelial growth factor (VEGF) play a key role in the development of DME and retinal NV. Studies in recent years have demonstrated that a number of endogenous angiogenic inhibitors are present in the normal retina and counter act the effect of VEGF in the regulation of angiogenesis and vascular permeability. Decreased levels of angiogenic inhibitors in the vitreous and retina have been found in diabetic patients and diabetic animal models. The decreased levels of angiogenic inhibitors shift the balance between angiogenic factors and angiogenic inhibitors and consequently, lead to the development of DME and retinal NV. Recently, we have found that these angiogenic inhibitors are expressed at high levels in the normal kidney and are down-regulated in diabetes. Moreover, these inhibitors inhibit the activity of VEGF and TGF-beta, two major pathogenic factors of DN. Therefore, decreased levels of these angiogenic inhibitors in diabetes may be associated with pathologies of DN. This review will summarize recent progress in these fields and therapeutic approaches to use angiogenic inhibitors for the treatment of diabetic complications.

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Therapeutic Potential of Angiostatin in Diabetic Nephropathy

Zhang¹,

Wang²,

Lu³

et al. 2006

Journal of the American Society of Nephrology

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Angiostatin is a proteolytic fragment of plasminogen and a potent angiogenic inhibitor. Previous studies have shown that angiostatin inhibits retinal neovascularization and reduces retinal vascular permeability in diabetic retinopathy. Here, it is reported for the first time that angiostatin is also implicated in diabetic nephropathy (DN). Angiostatin levels are dramatically decreased in the kidney of streptozotocin-induced diabetic rats. Consistently, diabetic kidneys also showed decreased expression and proteolytic activities of matrix metalloproteinase-2, an enzyme that releases angiostatin from plasminogen. Adenovirus-mediated delivery of angiostatin significantly alleviated albuminuria and attenuated the glomerular hypertrophy in diabetic rats. Moreover, angiostatin treatment downregulated the expression of vascular endothelial growth factor and TGF-␤1, two major pathogenic factors of DN, in diabetic kidneys. In cultured human mesangial cells, angiostatin blocked the overexpression of vascular endothelial growth factor and TGF-␤1 that were induced by high glucose while increasing the levels of pigment epithelium-derived factor, an endogenous inhibitor of DN. Moreover, angiostatin effectively inhibited the high-glucose-and TGF-␤1-induced overproduction of proinflammatory factors and extracellular matrix proteins via blockade of the Smad signaling pathway. These findings suggest that the decrease of angiostatin levels in diabetic kidney may contribute to the pathologic changes such as inflammation and fibrosis in DN. Therefore, angiostatin has therapeutic potential in DN as a result of its anti-inflammatory and antifibrosis activities.

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Targeting TGF could counter diabetic nephropathy

Cited by 5 publications

References 1 publication

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

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

Down-Regulation of Angiogenic Inhibitors: A Potential Pathogenic Mechanism for Diabetic Complications

Therapeutic Potential of Angiostatin in Diabetic Nephropathy

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