scholarly journals Thyroid hormone ameliorates diabetic nephropathy in a mouse model of type II diabetes

2011 ◽  
Vol 209 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Yi Lin ◽  
Zhongjie Sun
Keyword(s):  
Diabetic Nephropathy ◽  
Type Ii Diabetes ◽  
Structural Damage ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Diabetic Patients ◽  
Type Ii ◽  
Simultaneous Treatment ◽  
Pi3k Activity ◽  
Tgf Β1

Conventional therapies for diabetic patients, such as strict glycemic control, do not completely stop the progression of diabetic nephropathy. Serum-free tri-iodothyronine (T3) levels were lower in patients with type II diabetes. The purpose of this study was to test a hypothesis that treatment with T3 would improve diabetic nephropathy in db/db mice, a model of type II diabetes. Male db/db mice (16 weeks) were treated with T3 for 4 weeks. Urinary excretions of albumin and blood glucose levels were measured. Kidneys were collected for histological examination and molecular assays of transforming growth factor-β1 (TGF-β1) expression and phosphatidylinositol 3-kinase (PI3K). T3 attenuated albuminuria in db/db mice, suggesting an improved kidney function. T3 significantly decreased accumulation of collagenous components in cortical interstitium (interstitial fibrosis) and expansion of mesangial matrix in glomeruli (glomerulosclerosis) and prevented the loss of glomeruli in db/db mice. Therefore, T3 improved the renal structural damage seen in diabetic mice. Notably, diabetic nephropathy was accompanied by a significant decrease in PI3K activity and an increase in TGF-β1 expression in kidneys. T3 restored renal PI3K activity, attenuated hyperglycemia, and decreased renal TGF-β1 expression in db/db mice. These effects of T3 were abolished by simultaneous treatment with PI3K inhibitor (LY294002). These data suggest that T3 prevented progressive kidney damage and remodeling in db/db mice by improving insulin signaling (e.g. PI3K activity).

scholarly journals Dendrobium Mixture Improved Diabetic Nephropathy in db/db Mice by Regulating TGF-β1/Smads Signal Transduction

2021 ◽  
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Diabetic Nephropathy ◽  
Mrna Expression ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Fasting Blood Glucose ◽  
Blood Lipid ◽  
Control Group ◽  
Tgf Β1

Abstract BackgroundDendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. MethodsTwenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed using a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect mRNA expression of TGF-β1 and alpha-smooth muscle actin (α-SMA) genes and proteins, respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. ResultsDMix significantly reduced FBG level, BW, KW, and blood lipid level, and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced protein and mRNA expression of TGF-β1 and α-SMA, and inhibited Smad2 and Smad3 phosphorylation. ConclusionsThe findings suggest that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway. Key words: Diabetic nephropathy, Dendrobium mixture, TGF-β1/Smads signaling pathway

scholarly journals Protective Effects of Chromium Picolinate Against Diabetic-Induced Renal Dysfunction and Renal Fibrosis in Streptozotocin-Induced Diabetic Rats

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 398 ◽  
Author(s):  
Shan Shan Qi ◽  
Hong Xing Zheng ◽  
Hai Jiang ◽  
Li Ping Yuan ◽  
Le Chen Dong
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Biological Activities ◽  
Serum Insulin ◽  
Treated Group ◽  
Chromium Picolinate ◽  
Glomerular Sclerosis ◽  
Protective Effects ◽  
Tgf Β1

Diabetic nephropathy (DN) is one of the most important complications of diabetes, and the leading cause of end-stage renal disease (ESRD). While Chromium picolinate (CrPic) supplementation has been found to be effective in treating diabetes, its effects on diabetic-induced nephropathy have not been studied. Therefore, in this study, CrPic (1 mg kg−1 d−1) was administered to a DN rat model by oral gavage for eight weeks to investigate its effects. The results show that CrPic supplementation caused a decrease in levels of blood glucose, serum insulin, blood urea nitrogen (BUN), serum creatinine, and urinary albumin in DN rats. It also reversed renal pathological changes, including renal glomerular sclerosis and interstitial fibrosis. In addition, the oxidative defense system in the kidneys of DN rats was found to be improved; the biological activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) increased; and the content of malondialdehyde (MDA) lowered. Immunohistochemical results reveal that the expression levels of renal transforming growth factor-β1 (TGF-β1), Smad 2, and Smad 3 decreased significantly in the kidneys of rats in the CrPic-treated group. CrPic administration was thus found to ameliorate diabetic nephropathy in SD rats via an antioxidative stress mechanism, as well the ability to inhibit TGF-β1/Smad2/3 expression. This study suggests that CrPic could be a potential renal-protective nutrient against diabetic nephropathy.

scholarly journals Characterization of ferroptosis in kidney tubular cell death under diabetic conditions

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Seonghun Kim ◽  
Shin-Wook Kang ◽  
Jeongho Joo ◽  
Seung Hyeok Han ◽  
Huiyoon Shin ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Lipid Peroxide ◽  
Tubular Cell ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Glutathione Concentration ◽  
Tgf Β1

AbstractKidney tubular cell death induced by transforming growth factor-β1 (TGF-β1) is known to contribute to diabetic nephropathy, a major complication of diabetes. Caspase-3-dependent apoptosis and caspase-1-dependent pyroptosis are also involved in tubular cell death under diabetic conditions. Recently, ferroptosis, an atypical form of iron-dependent cell death, was reported to cause kidney disease, including acute kidney injury. Ferroptosis is primed by lipid peroxide accumulation through the cystine/glutamate antiporter system Xc− (xCT) and glutathione peroxidase 4 (GPX4)-dependent mechanisms. The aim of this study was to evaluate the role of ferroptosis in diabetes-induced tubular injury. TGF-β1-stimulated proximal tubular epithelial cells and diabetic mice models were used for in vitro and in vivo experiments, respectively. xCT and GPX4 expression, cell viability, glutathione concentration, and lipid peroxidation were quantified to indicate ferroptosis. The effect of ferroptosis inhibition was also assessed. In kidney biopsy samples from diabetic patients, xCT and GPX4 mRNA expression was decreased compared to nondiabetic samples. In TGF-β1-stimulated tubular cells, intracellular glutathione concentration was reduced and lipid peroxidation was enhanced, both of which are related to ferroptosis-related cell death. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, alleviated TGF-β1-induced ferroptosis. In diabetic mice, kidney mRNA and protein expressions of xCT and GPX4 were reduced compared to control. Kidney glutathione concentration was decreased, while lipid peroxidation was increased in these mice, and these changes were alleviated by Fer-1 treatment. Ferroptosis is involved in kidney tubular cell death under diabetic conditions. Ferroptosis inhibition could be a therapeutic option for diabetic nephropathy.

scholarly journals Vitamin D in Different Stages of Type 2 Diabetic Nephropathy and its Correlation with Transforming Growth Factor Beta-1 (TGF-β1) –A Cross Sectional Study

2021 ◽  
pp. 141-147
Author(s):  
Liji Kavuparambil ◽  
Ashok Kumar Pammi ◽  
T. K. Jithesh ◽  
K. Shifa
Keyword(s):  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Diabetic Patients ◽  
Vitamin D Status ◽  
Cross Sectional ◽  
Growth Factor Beta ◽  
Tgf Β1

Background: Diabetic nephropathy (DN) is a microvascular complication of Diabetes Mellitus (DM) and the prevalence of which is increasing in every year. Monitoring of Vitamin D status in diabetic nephropathy patients is important, as the deficiency of vitamin D appears as a risk factor for the development of diabetic nephropathy. Studies evaluating the role of vitamin D in DN are few. Conflicting data is available on the correlation between vitamin D and Diabetic Nephropathy. Studies revealed the sample population is Vitamin D deficient. Therefore, it is important to understand the correlation of Vitamin D with severity of Diabetic nephropathy and its role in fibrogenesis. The aim of this study is to analyse vitamin D status in different stages of type 2 diabetic nephropathy and its correlation with transforming growth factor beta-1. Methods: A 1.5-year cross-sectional study of 120 diabetic patients, 60 with nephropathy and 60 without nephropathy patients enrolled to MES Medical College. Patients with heart, liver, or thyroid disease, as well as those on dialysis, were excluded from the study. The VITROS 5600 integrated system were used to measure fasting blood sugar (FBS), HbA1c, creatinine and vitamin D.  Transforming Growth Factor Beta-1 (TGF-β1) is measured using ELISA technique. According to HbA1c and estimated glomerular filtration rate (eGFR) values, the study population is divided into two groups. The statistical package for the social sciences (SPSS) software was used to conduct the analysis. The level of significance was calculated at 95%. Results: The level of vitamin D in diabetic patients with nephropathy is much lower than in diabetic patients without nephropathy. In diabetic nephropathy patients, serum creatinine, urea, HbA1c and TGF-β1 exhibited a highly significant negative correlation with vitamin D status, but eGFR showed a highly significant positive correlation. Conclusion: Vitamin D status has been found to be poor in all diabetic patients, with a greater drop in diabetic nephropathy patients. In diabetic nephropathy patients, serum creatinine, urea, HbA1c and TGF-β1 exhibited a highly significant negative association with vitamin D status, but eGFR showed a highly significant positive link. Deficiency of vitamin D have role in the development and severity of DN, and showed a highly significant correlation with the regulator of fibrosis, TGF-β1. This finding indicates that vitamin D couldbe an important factor for development and progression of Diabetic nephropathy. So supplementation of vitamin D may slow down progression of DN. 

scholarly journals Dendrobium Mixture Ameliorates Diabetic Nephropathy in db/db Mice by Regulating the TGF-β1/Smads Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yong Chen ◽  
Xiaohui Lin ◽  
Yanfang Zheng ◽  
Wenzhen Yu ◽  
Fan Lin ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Lipid Level ◽  
Fasting Blood Glucose ◽  
Blood Lipid ◽  
Control Group ◽  
Expression Levels ◽  
Tgf Β1

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-β1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-β1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway.

scholarly journals NQO1 Deficiency Aggravates Renal Injury by Dysregulating Vps34/ATG14L Complex during Autophagy Initiation in Diabetic Nephropathy

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 333
Author(s):  
Geum-Lan Hong ◽  
Kyung-Hyun Kim ◽  
Chul-Ho Lee ◽  
Tae-Won Kim ◽  
Ju-Young Jung
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor Beta ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Cell Damage ◽  
End Stage ◽  
Hk2 Cells ◽  
Tgf Β1

Diabetic nephropathy (DN) is one of the causes of end-stage renal failure, featuring renal fibrosis. However, autophagy, a vital process for intracellular homeostasis, can counteract renal fibrosis. Moreover, NAD(P)H: quinone dehydrogenase 1 (NQO1) modulates the ratios of reduced/oxidized nicotinamide nucleotides, exerting a cytoprotective function. Here, to examine the role of NQO1 genes in DN progression, the levels of autophagy-related proteins and pro-fibrotic markers were assessed in silencing or overexpression of NQO1 in human proximal tubular cells (HK2), and C57BL/6 (wild-type) and Nqo1 knockout (KO) mice injected to streptozotocin (50 mg/kg). NQO1 deficiency impaired the autophagy process by suppressing basal expression of ClassⅢ PI 3-kinase (Vps34) and autophagy-related (ATG)14L and inducing the expressions of transforming growth factor beta (TGF-β1), Smad3, and matrix metallopeptidase9 (MMP9) in high-glucose (HG) -treated HK2 cells. Meanwhile, NQO1 overexpression increased the expression of Vps34 and ATG14L, while, reducing TGF-β1, Smad3 and MMP9 expression. In vivo, the expression of Vps34 and ATG14L were suppressed in Nqo1 KO mice indicating aggravated glomerular changes and interstitial fibrosis. Therefore, NQO1 deficiency dysregulated autophagy initiation in HK2 cells, with consequent worsened renal cell damage under HG condition. Moreover, STZ-treated Nqo1 KO mice showed that NQO1 deficiency aggravated renal fibrosis by dysregulating autophagy.

Relationship between uric acid and creatinine in pre-diabetic and diabetic patients: Vidarbha region of Maharashtra

2020 ◽  
Vol 11 (3) ◽  
pp. 3412-3417
Author(s):  
Ranjit S. Ambad ◽  
Rakesh Kumar Jha ◽  
Lata Kanyal Butola ◽  
Nandkishor Bankar ◽  
Brij Raj Singh ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Type Ii Diabetes ◽  
Fasting Blood Glucose ◽  
General Medicine ◽  
Control Group ◽  
Diabetic Patients ◽  
Type Ii ◽  
Develop Type ◽  
Low Levels

Prediabetes is a glucose homeostasis condition characterized by decreased absorption to glucose or reduced fasting glucose. Both of these are reversible stages of intermediate hyperglycaemia providing an increased type II DM risk. Pre-diabetes can therefore be viewed as a significant reversible stage which could lead to type II DM, and early detection of prediabetes may contribute to type II DM prevention. Prediabetes patients are at high risk for potential type II diabetes, and 70 percent of them appear to develop Type II diabetes within 10 years. The present study includes total 200 subjects that include 100 Prediabetic patients, 50 T2DM patients and 50 healthy individual. Blood samples were collected from the subjects were obtained for FBS, PPBS, Uric acid and Creatinine estimation, from OPD and General Medicine Wards. Present study showed low levels of Serum Uric Acid in prediabetic and T2DM patients were decreased as compared to control group, while the level of creatinine in prediabetic and diabetic were elevated as compared to control group, were not statically significant. Serum Uric Acid was high in control group and low in prediabetic and diabetic patients. Serum creatinine was declined in control group and increased in prediabetic and diabetic patients with increasing Fasting blood glucose level.

Regulation of extracellular matrix synthesis by TNF-α and TGF-β1 in type II cells exposed to coal dust

1998 ◽  
Vol 275 (4) ◽  
pp. L637-L644 ◽  
Author(s):  
Yu-Chen Lee ◽  
D. Eugene Rannels
Keyword(s):  
Extracellular Matrix ◽  
Cell Cultures ◽  
Transforming Growth Factor ◽  
Coal Dust ◽  
Transforming Growth Factor Β1 ◽  
Type Ii ◽  
Tnf Α ◽  
Type Ii Cell ◽  
Primary Type ◽  
Tgf Β1

Type II pulmonary epithelial cells respond to anthracite coal dust PSOC 867 with increased synthesis of extracellular matrix (ECM) components. Alveolar macrophages modulate this response by pathways that may involve soluble mediators, including tumor necrosis factor-α (TNF-α) or transforming growth factor-β1 (TGF-β1). The effects of TNF-α (10 ng/ml) and/or TGF-β1 (2 ng/ml) were thus investigated in dust-exposed primary type II cell cultures. In control day 1 or day 3 cultures, TNF-α and/or TGF-β1 had little or no effect on the synthesis of type II cellular proteins, independent of whether the cells were exposed to dust. With PSOC 867 exposure, where ECM protein synthesis is elevated, TNF-α and TGF-β1 further increased both the absolute and relative rates of ECM synthesis on day 3 but had little effect on day 1. Each mediator increased expression of fibronectin mRNA, as well as of ECM fibronectin content, in a manner qualitatively similar to their effects on synthesis. Thus TNF-α and TGF-β1 modulate both ECM synthesis and fibronectin content in coal dust-exposed type II cell cultures.

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