Mechanical forces and TGF 1 reduce podocyte adhesion through  3 1 integrin downregulation

Dessapt, Cecile; Baradez, Marc‐Olivier; Hayward, A; Dei, Alessandra; Thomas, Stephen; Viberti, Giancarlo; Gnudi, Luigi

doi:10.1093/ndt/gfp204

Cited by 84 publications

(74 citation statements)

References 54 publications

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“…Chen et al (6) showed that decreased expression of α3β1 integrin in podocytes was closely related to podocyte depletion, glomerular sclerosis, and daily protein loss in patients with primary FSGS and chronic PAN-treated rats. Down-regulation of α3β1 integrin expression is per se sufficient to reduce podocyte adhesion (27). α-DG was found to play important roles in maintaining unique architecture of podocytes by binding to the GBM, and in maintaining the integrity of filtration slit through negatively charged sialic acid residues (28).…”

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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“…Detached cells are shed in the urine as live podocytes (Petermann et al, 2003). Loss of cell anchorage to the GBM may result from down-regulation of the ␣ 3 ␤ 1 integrins (Dessapt et al, 2009) and increased levels of TGF-␤1 (Chen et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Distinct Actions of Endothelin A-Selective Versus Combined Endothelin A/B Receptor Antagonists in Early Diabetic Kidney Disease

Saleh

Pollock²,

Pollock³

2011

J Pharmacol Exp Ther

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Selective endothelin A (ET A ) and combined ET A and ET B receptor antagonists are being investigated for use in treating diabetic nephropathy. However, the receptor-specific mechanisms responsible for producing the potential benefits have not been discerned. Thus, we determined the actions of ET A and ET B receptors on measures of glomerular function and renal inflammation in the early stages of diabetic renal injury in rats through the use of selective and combined antagonists. Six weeks after streptozotocin (STZ)-induced hyperglycemia, rats were given 2R-(4-pyrrolidine-3-carboxylic acid hydrochloride (A-182086) (10 mg/kg/day), a combined ET A/B antagonist; or vehicle for 1 week. Sham controls received STZ vehicle (saline). Hyperglycemia led to significant proteinuria, increased glomerular permeability to albumin (P alb ), nephrinuria, and an increase in total matrix metalloprotease (MMP) and transforming growth factor-␤1 (TGF-␤1) activities in glomeruli. Plasma and glomerular soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were elevated after 7 weeks of hyperglycemia. Daily administration of both ABT-627 and A-182086 for 1 week significantly attenuated proteinuria, the increase in P alb , nephrinuria, and total MMP and TGF-␤1 activity. However, glomerular sICAM-1 and MCP-1 expression was attenuated with ABT-627, but not A-182086, treatment. In summary, both selective ET A and combined ET A/B antagonists reduced proteinuria and glomerular permeability and restored glomerular filtration barrier component integrity, but only ET A -selective blockade had antiinflammatory and antifibrotic effects. We conclude that selective ET A antagonists are more likely to be preferred for the treatment of diabetic kidney disease.

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“…Decreased expression of α 3 β 1 integrin expression in podocytes may serve to foot process detachment, podocyte loss and proteinuria in humans with primary FSGS and chronic PAN-treated rats [28]. Previous study reported that downregulation of α 3 β 1 integrin expression, by mechanical forces or TGFβ1, was per se sufficient to decrease podocyte adhesion in vitro , which contributed to the elucidation of the mechanisms of the podocyte detachment from the GBM observed in diabetes and other glomerular diseases [29]. In vitro study has demonstrated that high glucose reduces expression of α 3 β 1 integrin in cultured human glomerular epithelial cells, accompanied by decreased binding of these cells to type IV collagen [10].…”

Section: Discussionmentioning

confidence: 99%

Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through a₃�₁Integrin Upregulationin Vitroandin Vivo

Gui

Li²,

Guo³

et al. 2014

Cell Physiol Biochem

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Background: Decreased expression of α₃β₁ integrin may contribute to reduction in podocyte adhesion to glomerular basement membrane (GBM), which represents a novel early mechanism leading to diabetic kidney disease (DKD). Here, we examined the protective effects of Notoginsenoside R1 (NR1) on podocyte adhesion and α₃β₁ integrin expression under diabetic condition in vitro and in vivo. Methods: Conditionally immortalized mouse podocytes were exposed to high glucose (HG) with 10 and 100μg /ml of NR1 for 24 h. Podocyte adhesion, albuminuria, oxidative markers, renal histopathology, podocyte number per glomerular volume, integrin-linked kinase (ILK) activity and α₃β₁ integrin expression were measured in vitro and in vivo. Results: HG decreased podocyte adhesive capacity and α₃β₁ integrin expression, the main podocyte anchoring dimer to the GBM. However, NR1 ameliorated impaired podocyte adhesive capacity and partially restored α₃β₁ integrin protein and mRNA expression. These in vitro observations were confirmed in vivo. In streptozotocin(STZ)-induced diabetic rats, treatment with NR1 (5 and 10 mg· kg^-1· d^-1) for 12 weeks partially restored the number of podocytes per glomerular volume and glomerular α₃β₁ integrin expression, as well as ameliorated albuminuria, histopathology and oxidative stress. NR1 also inhibited glomerular ILK activity in diabetic rats. Conclusion: NR1, a novel antioxidant, ameliorated glucose-induced impaired podocyte adhesive capacity and subsequent podocyte depopulation partly through α₃β₁ integrin upregulation. These findings might provide a potential new therapeutic option for the treatment of DKD.

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Mechanical forces and TGF 1 reduce podocyte adhesion through 3 1 integrin downregulation

Abstract: These results suggest that downregulation of alpha3beta1 integrin expression, by mechanical forces or TGFbeta1, is per se sufficient to reduce podocyte adhesion. Apoptosis may represent a parallel important determinant of the podocyte loss from the GBM.

Cited by 84 publications

References 54 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

Distinct Actions of Endothelin A-Selective Versus Combined Endothelin A/B Receptor Antagonists in Early Diabetic Kidney Disease

Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through a₃�₁Integrin Upregulationin Vitroandin Vivo

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Mechanical forces and TGF 1 reduce podocyte adhesion through 3 1 integrin downregulation

Abstract: These results suggest that downregulation of alpha3beta1 integrin expression, by mechanical forces or TGFbeta1, is per se sufficient to reduce podocyte adhesion. Apoptosis may represent a parallel important determinant of the podocyte loss from the GBM.

Cited by 84 publications

References 54 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

Distinct Actions of Endothelin A-Selective Versus Combined Endothelin A/B Receptor Antagonists in Early Diabetic Kidney Disease

Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through a3�1Integrin Upregulationin Vitroandin Vivo

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Notoginsenoside R1 Ameliorates Podocyte Adhesion Under Diabetic Condition Through a₃�₁Integrin Upregulationin Vitroandin Vivo