Altering expression of α3β1 integrin on podocytes of human and rats with diabetes

Chen, Hung‐Chun; Chen, Chain-Ann; Guh, Jinn‐Yuh; Chang, Jer‐Ming; Shin, Shyi–Jang; Lai, Yung‐Hsiung

doi:10.1016/s0024-3205(00)00815-8

Cited by 102 publications

(85 citation statements)

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“…Anti-β1 integrin antibodies lead to an increase of albumin permeability in isolated glomeruli (19). Reduced expression of α3β1 integrin in podocytes has been demonstrated in both humans with FSGS (6) and in diabetic (20) and PAN model rats (21). Podocyte foot processes are anchored to the GBM via α3β1 integrin (22) and α/β-DG (23).…”

Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

Min-shu

Zhou

et al. 2010

Intern. Med.

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Objective To investigate the role of α3β1 integrin and α/β-dystroglycan in protective effects of 1,25(OH)2D3 on podocytes in rats with adriamycin-induced nephropathy. Methods Sprague-Dawley rats were randomly divided into three groups: control group (NC), nephropathy group (NE), and nephropathy+1,25(OH)2D3 group (ND). Rats in NE and ND group were injected intravenously with adriamycin (0.1 mg/10 g body weight) to induce nephropathy, and those in ND group were then subcutaneously treated with 1,25(OH)2D3 for 8 weeks. Urinary protein level, number of urine podocytes, foot process width and glomerulosclerotic index were determined. Nephrin and podocin mRNA and protein expressions were determined by RT-PCR and western blot, respectively. Podocyte density and expressions of α3β1 integrin and α/β-dystroglycan (DG) were analyzed by immunohistochemistry and western blot, respectively. Results The increase in proteinuria, podocyturia and width of foot process in NE group were ameliorated after treatment with 1,25(OH)2D3 for 8 weeks. The glomerulosclerotic index was significantly decreased in ND group when compared with NE group. The podocyte density in ND group (10.3 ± 1.64 cells/glomerulus) was significantly higher than that in NE group (8.43 ± 1.75 cells/glomerulus) (p=0.008). 1,25(OH)2D3 treatment could significantly up-regulate the mRNA and protein expressions of nephrin and podocin, and the protein expressions of α3β1 integrin and α/β-DG. Conclusion The expressions of nephrin, podocin, α3β1 integrin and α/β-DG were decreased in rats with nephropathy. However, 1,25(OH)2D3 treatment could significantly up-regulate the expressions of nephrin, podocin, α3β1 integrin and α/β-DG proteins which might suppress podocyte detachment and podocytopenia.

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Section: Discussionmentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

Min-shu

Zhou

et al. 2010

Intern. Med.

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“…At normal glucose concentration, the interaction with collagen IV was mediated mainly by the α3β1 and α2β1 and to a lesser extent by α5β1 integrins, whereas at high glucose concentration the expression of αvβ3 and α5β1 integrins was upregulated ( Figure 2) [7,8]. It has been reported in streptozotocindiabetic rats, that the expression of α3β1 integrin, which is the main integrin occurring at the interface between the foot process and the GBM, was decreased in comparison to the normal control rate [9,10]. Accordingly, glomerular epithelial cells cultured in high glucose showed reduced expression of the α3, α2, and β1 integrin subunits in combination with increased expression of α5 and αvβ3 integrins [7].…”

Section: Glomerular Basement Membrane (Gbm)mentioning

confidence: 97%

Microvascular basement membranes in diabetes mellitus

Tsilibary

2003

The Journal of Pathology

242

156

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The alterations in the microvascular system of diabetes mellitus patients are responsible for the most devastating complications of this widespread disease. In the kidney, the microangiopathy leads to thickening of the glomerular capillary basement membrane but also to the expansion of the mesangial matrix and thickening of the tubular basement membrane. Several mechanisms are implicated in the pathogenesis of diabetic renal microangiopathy. These include increased synthesis of type IV collagen following hyperglycaemia-induced alteration of the pattern of podocyte-integrin expression, decreased expression of matrix metalloproteinases (MMP-2 and 3), and increased expression of tissue inhibitor of metalloproteinase (TIMP). An altered morphology of podocytes accompanies these basement membrane alterations. Other factors which may contribute to renal matrix accumulation include vascular endothelial growth factor (VEGF), since treatment with anti-VEGF antibodies attenuates glomerular basement membrane thickening, platelet-derived growth factor (PDGF) (B chain) and its receptor, which appear to be highly expressed in mesangial and visceral epithelial cells and might play a role in the development of diabetic nephropathy. Also oxygen radicals/oxidative stress may play a role in matrix accumulation in diabetic nephropathy as aminoguanidine, an inhibitor of the formation of advanced glycation endproducts but with antioxidant properties, attenuates diabetic nephropathy. Retinal diabetic microangiopathy follows much the same principles, be it that microvascular proliferation is a distinctive element in the retina. Nephropathy and retinopathy occur frequently but not always together, indicating that in their multifactorial pathogenesis much remains to be clarified.

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“…The integrin ␣3␤1 is an adhesion molecule, which is primarily involved in podocyte adhesion to the glomerular basement membrane. 68 The expression of ␣3␤1integrin is reduced in vitro in podocytes exposed to high glucose and in vivo in podocytes not only from streptozotocin-induced diabetic rats but also in patients with diabetic nephropathy. 68 Preliminary evidence suggests that mechanical stretch may reduce both the expression of the integrin ␣3␤1 and podocyte adhesion to an extracellular matrix substrate, 69 providing a mechanism whereby glomerular capillary hypertension may favor the detachment of podocytes from the glomerular basement membrane.…”

Section: The Role Of Glomerular Capillary Hypertensionmentioning

confidence: 98%

Mechanisms of Diabetic Nephropathy

Giunti¹,

Barit²,

Cooper³

2006

Hypertension

138

102

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D iabetic nephropathy is a major microvascular complication of diabetes, representing the leading cause of endstage renal disease in the Western world, and a major cause of morbidity and mortality in both type 1 and type 2 diabetic subjects. Clinical hallmarks of diabetic nephropathy include a progressive increase in urinary albumin excretion and a decline in glomerular filtration rate (GFR), which occur in association with an increase in blood pressure, ultimately leading to endstage renal failure. 1 These renal functional changes develop as a consequence of structural abnormalities, including glomerular basement membrane thickening, mesangial expansion with extracellular matrix accumulation, changes in glomerular epithelial cells (podocytes), including a decrease in number and/or density, podocyte foot process broadening and effacement, glomerulosclerosis, and tubulointerstitial fibrosis.Diabetic nephropathy occurs only in a minority of subjects with either type 1 or type 2 diabetes and seems to result from the interaction between genetic susceptibility and environmental insults, primarily metabolic and hemodynamic in origin. Over the last decade, the cellular and molecular mechanisms by which these insults translate to structural and functional abnormalities leading to diabetic nephropathy have been increasingly delineated. In particular, it has been determined that both metabolic and hemodynamic stimuli lead to the activation of key intracellular signaling pathways and transcription factors, thus triggering the production/release of cytokines, chemokines, and growth factors, which mediate and/or amplify renal damage.In the present review, we summarize molecular and cellular mechanisms that seem to be responsible for hypertensioninduced renal injury in diabetes, with particular focus on the role of increased intracapillary glomerular pressure, more recently discovered components of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) 2, and the increasing knowledge that has been gained emphasizing cross-talk between metabolic and hemodynamic pathways in amplifying diabetes-related renal injury. Impact of Hypertension on Diabetic NephropathyThe relationship between hypertension and poor vascular outcomes, including progression of renal disease, is unequivocal and independent of other confounding factors. The impact of hypertension on outcomes is exponential rather than linear. A sustained reduction in blood pressure seems to be currently the most important single intervention to slow progressive nephropathy in type 1 and type 2 diabetes. Long-term follow-up studies of initially normotensive diabetic subjects without renal disease demonstrate a blood pressure-dependent decline in GFR with blood pressure levels within the reference range. 2 Patients with a blood pressure corresponding to Ͻ130/80 mm Hg rarely develop microalbuminuria and show an annual decline in GFR close to the age-matched normal population. Diabetic patients with a blood pressure between 130/80 and 140/90 mm Hg have ...

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Altering expression of α3β1 integrin on podocytes of human and rats with diabetes

Cited by 102 publications

References 0 publications

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

1,25-Dihydroxyvitamin D3 Ameliorates Podocytopenia in Rats with Adriamycin-induced Nephropathy

Microvascular basement membranes in diabetes mellitus

Mechanisms of Diabetic Nephropathy

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