Renal connective tissue growth factor correlates with glomerular basement membrane thickness and prospective albuminuria in a non-human primate model of diabetes: possible predictive marker for incipient diabetic nephropathy

2008 ◽  
Vol 22 (4) ◽  
pp. 284-294 ◽  
Author(s):  
Sally E. Thomson ◽  
Susan V. McLennan ◽  
Paul D. Kirwan ◽  
Scott J. Heffernan ◽  
Annemarie Hennessy ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Predictive Marker ◽  
Tissue Growth ◽  
Membrane Thickness ◽  
Primate Model ◽  
Basement Membrane Thickness ◽  
Incipient Diabetic Nephropathy ◽  
Glomerular Basement Membrane Thickness ◽  
Human Primate

scholarly journals Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy

2019 ◽  
Vol 10 (1) ◽  
pp. 216-226 ◽  
Author(s):  
Ghada Alomari ◽  
Bahaa Al-Trad ◽  
Salehhuddin Hamdan ◽  
Alaa Aljabali ◽  
Mazhar Al-Zoubi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gold Nanoparticles ◽  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Protein Expression ◽  
Male Rats ◽  
Extracellular Matrix Protein ◽  
Membrane Thickness ◽  
Podocyte Injury ◽  
Basement Membrane Thickness

Abstract Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.

scholarly journals Effect of Pinocembrin Isolated from Mexican Brown Propolis on Diabetic Nephropathy

Molecules ◽  
2018 ◽  
Vol 23 (4) ◽  
pp. 852 ◽  
Author(s):  
Jessica Granados-Pineda ◽  
Norma Uribe-Uribe ◽  
Patricia García-López ◽  
María Ramos-Godinez ◽  
J. Rivero-Cruz ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Lipid Profile ◽  
Filtration Rate ◽  
Renal Damage ◽  
Antioxidant Activities ◽  
Kidney Damage ◽  
Membrane Thickness ◽  
Basement Membrane Thickness ◽  
Glomerular Basement Membrane Thickness

Propolis is a resinous beehive product that has been used worldwide in traditional medicine to prevent and treat colds, wounds, rheumatism, heart disease and diabetes. Diabetic nephropathy is the final stage of renal complications caused by diabetes and for its treatment there are few alternatives. The present study aimed to determine the chemical composition of three propolis samples collected in Chihuahua, Durango and Zacatecas and to evaluate the effect of pinocembrin in a model of diabetic nephropathy in vivo. Previous research demonstrated that propolis of Chihuahua possesses hypoglycemic and antioxidant activities. Two different schemes were assessed, preventive (before renal damage) and corrective (once renal damage is established). In the preventive scheme, pinocembrin treatment avoids death of the rats, improves lipid profile, glomerular filtration rate, urinary protein, avoid increases in urinary biomarkers, oxidative stress and glomerular basement membrane thickness. Whereas, in the corrective scheme, pinocembrin only improves lipid profile without showing improvement in any other parameters, even pinocembrin exacerbated the damage. In conclusion, pinocembrin ameliorates diabetic nephropathy when there is no kidney damage but when it is already present, pinocembrin accelerates kidney damage.

scholarly journals Blocking Ligand Occupancy of the αVβ3 Integrin Inhibits the Development of Nephropathy in Diabetic Pigs

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4665-4675 ◽  
Author(s):  
Laura A. Maile ◽  
Walker H. Busby ◽  
Katherine A. Gollahon ◽  
William Flowers ◽  
Nikol Garbacik ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Diabetic Nephropathy ◽  
Basement Membrane ◽  
Treated Group ◽  
Membrane Thickness ◽  
Αvβ3 Integrin ◽  
Basement Membrane Thickness ◽  
Foot Process ◽  
Histologic Changes ◽  
Glomerular Basement Membrane Thickness

Hyperglycemia stimulates secretion of αVβ3 ligands from vascular cells, including endothelial cells, resulting in activation of the αVβ3 integrin. This study determined whether blocking ligand occupancy of αVβ3 would inhibit the development of diabetic nephropathy. Ten diabetic pigs received an F(ab)2 fragment of an antibody directed against the extracellular domain of the β3-subunit, and 10 received a control IgG F(ab)2 for 18 weeks. Nondiabetic pigs excreted 115 ± 50 μg of protein/mg creatinine compared with control F(ab)2-treated diabetic animals (218 ± 57 μg/mg), whereas diabetic animals treated with the anti-β3 F(ab)2 excreted 119 ± 55 μg/mg (P < .05). Mesangial volume/glomerular volume increased to 21 ± 2.4% in control-treated diabetic animals compared with 14 ± 2.8% (P < .01) in animals treated with active antibody. Diabetic animals treated with control F(ab)2 had significantly less glomerular podocin staining compared with nondiabetic animals, and this decrease was attenuated by treatment with anti-β3 F(ab)2. Glomerular basement membrane thickness was increased in the control, F(ab)2-treated diabetic animals (212 ± 14 nm) compared with nondiabetic animals (170 ± 8.8 nm), but it was unchanged (159.9 ± 16.4 nm) in animals receiving anti-β3 F(ab)2. Podocyte foot process width was greater in control, F(ab)2-treated, animals (502 ± 34 nm) compared with animals treated with the anti-β3 F(ab)2 (357 ± 47 nm, P < .05). Renal β3 tyrosine phosphorylation decreased from 13 934 ± 6437 to 6730 ± 1524 (P < .01) scanning units in the anti-β3-treated group. We conclude that administration of an antibody that inhibits activation of the β3-subunit of αVβ3 that is induced by hyperglycemia attenuates proteinuria and early histologic changes of diabetic nephropathy, suggesting that it may have utility in preventing the progression of this disease complication.

scholarly journals Connective tissue growth factor in tubulointerstitial injury of diabetic nephropathy

2001 ◽  
Vol 60 (1) ◽  
pp. 96-105 ◽  
Author(s):  
Shinong Wang ◽  
Mark Denichilo ◽  
Carrie Brubaker ◽  
Raimund Hirschberg
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Tissue Growth ◽  
Tubulointerstitial Injury

Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy

2001 ◽  
Vol 359 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Nadia Abdel WAHAB ◽  
Natalia YEVDOKIMOVA ◽  
Benjamin S. WESTON ◽  
Terry ROBERTS ◽  
Xin Jun LI ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Connective Tissue ◽  
High Glucose ◽  
Mesangial Cell ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

We characterized a rabbit polyclonal antibody raised against human recombinant connective tissue growth factor (CTGF). The antibody recognised a higher molecular mass form (approx. 56kDa) of CTGF in mesangial cell lysates as well as the monomeric (36–38kDa) and lower molecular mass forms (< 30kDa) reported previously. Immunohistochemistry detected CTGF protein in glomeruli of kidneys of non-obese diabetic mice 14 days after the onset of diabetes, and this was prominent by 70 days. CTGF protein is also present in glomeruli of human patients with diabetic nephropathy. No CTGF was detected in either normal murine or human glomeruli. Transient transfection of a transformed human mesangial cell line with a CTGF–V5 epitope fusion protein markedly increased fibronectin and plasminogen activator inhibitor-1 synthesis in cultures maintained in normal glucose (4mM) conditions; a CTGF-antisense construct reduced the elevated synthesis of these proteins in high glucose (30mM) cultures. Culture of primary human mesangial cells for 14 days in high glucose, or in low glucose supplemented with recombinant CTGF or transforming growth factor β1, markedly increased CTGF mRNA levels and fibronectin synthesis. However, whilst co-culture with a CTGF-antisense oligonucleotide reduced the CTGF mRNA pool by greater than 90% in high glucose, it only partially reduced fibronectin mRNA levels and synthesis. A chick anti-CTGF neutralizing antibody had a similar effect on fibronectin synthesis. Thus both CTGF and CTGF-independent pathways mediate increased fibronectin synthesis in high glucose. Nevertheless CTGF expression in diabetic kidneys is likely to be a key event in the development of glomerulosclerosis by affecting both matrix synthesis and, potentially through plasminogen activator inhibitor-1, its turnover.

scholarly journals Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy

2020 ◽  
Vol 21 (12) ◽  
pp. 4225
Author(s):  
Lucas Opazo-Ríos ◽  
Anita Plaza ◽  
Yenniffer Sánchez Matus ◽  
Susana Bernal ◽  
Laura Lopez-Sanz ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Binding Domain ◽  
Inflammatory Factors ◽  
Preclinical Model ◽  
Membrane Thickness ◽  
Basement Membrane Thickness ◽  
Nemo Binding Domain ◽  
Nbd Peptide

Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN.

scholarly journals Transgenic overexpression of GLUT1 in mouse glomeruli produces renal disease resembling diabetic glomerulosclerosis

2010 ◽  
Vol 299 (1) ◽  
pp. F99-F111 ◽  
Author(s):  
Youli Wang ◽  
Kathleen Heilig ◽  
Thomas Saunders ◽  
Andrew Minto ◽  
Dilip K. Deb ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Glomerular Disease ◽  
Membrane Thickness ◽  
Renal Tubules ◽  
Glomerular Mesangial Cells ◽  
Diabetic Glomerulosclerosis ◽  
Basement Membrane Thickness ◽  
Intracellular Glucose

Previous work identified an important role for hyperglycemia in diabetic nephropathy (The Diabetes Control and Complications Trial Research Group. N Engl J Med 329: 977–986, 1993; UK Prospective Diabetes Study Group. Lancet 352: 837–853, 1998), and increased glomerular GLUT1 has been implicated. However, the roles of GLUT1 and intracellular glucose have not been determined. Here, we developed transgenic GLUT1-overexpressing mice (GT1S) to characterize the roles of GLUT1 and intracellular glucose in the development of glomerular disease without diabetes. GLUT1 was overexpressed in glomerular mesangial cells (MC) of C57BL6 mice, a line relatively resistant to diabetic nephropathy. Blood pressure, blood glucose, glomerular morphometry, matrix proteins, cell signaling, transcription factors, and selected growth factors were examined. Kidneys of GT1S mice overexpressed GLUT1 in glomerular MCs and small vessels, rather than renal tubules. GT1S mice were neither diabetic nor hypertensive. Glomerular GLUT1, glucose uptake, mean capillary diameter, and mean glomerular volume were all increased in the GT1S mice. Moderately severe glomerulosclerosis (GS) was established by 26 wk of age in GT1S mice, with increased glomerular type IV collagen and fibronectin. Modest increases in glomerular basement membrane thickness and albuminuria were detected with podocyte foot processes largely preserved, in the absence of podocyte GLUT1 overexpression. Activation of glomerular PKC, along with increased transforming growth factor-β1, VEGFR1, VEGFR2, and VEGF were all detected in glomeruli of GT1S mice, likely contributing to GS. The transcription factor NF-κB was also activated. Overexpression of glomerular GLUT1, mimicking the diabetic GLUT1 response, produced numerous features typical of diabetic glomerular disease, without diabetes or hypertension. This suggested GLUT1 may play an important role in the development of diabetic GS.

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