Regulation of Glomerular Epithelial Cell Production of Fibronectin and Transforming Growth Factor-β by High Glucose, Not by Angiotensin II

Det, Nicole F. van; Verhagen, Nicole A.M.; Tamsma, J. T.; Berden, J.H.M.; Bruijn, Jan A.; Daha, Mohamed R.; Woude, Fokko J. van der

doi:10.2337/diab.46.5.834

Cited by 48 publications

(27 citation statements)

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“…However, a lack of expression of ANG II receptors in undifferentiated human and mouse podocytes has been reported in several studies (278,475). In the latter study, no mRNA for AT 1 or AT 2 receptors, besides mRNA expression for ANG II degrading hydrolase aminopeptidase A and angiotensinogen, was detected in cultured undifferentiated mouse podocytes (278).…”

Section: Ca 2؉ Signalingmentioning

confidence: 87%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,308

1,278

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Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. New technical approaches have led to a considerable increase in our understanding of podocyte biology including protein inventory, composition and arrangement of the cytoskeleton, receptor equipment, and signaling pathways involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of acquired glomerular disease. In hereditary nephrotic syndromes identified over the last 2 years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

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Section: Ca 2؉ Signalingmentioning

confidence: 87%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,308

1,278

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“…Experimental hyperglycemia can increase TGF-␤1 production either directly (14)(15)(16)(17) or through the formation of advanced glycated end products (18) in the kidney cell culture. However, glycemic control did not predict urinary TGF-␤1 levels in adult type 1 diabetic patients (19).…”

Section: Urinary Aermentioning

confidence: 99%

Urinary transforming growth factor-beta1 and alpha1-microglobulin in children and adolescents with type 1 diabetes.

Korpinen

Teppo²,

Hukkanen³

et al. 2000

Diabetes Care

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“…3,4 The possible importance of TGF-␤1 in diabetic nephropathy has been demonstrated in vitro by glucose-induced upregulation of this cytokine in different cell types. [5][6][7][8][9][10][11][12][13] Increased TGF-␤1 expression has also been demonstrated in diabetic animal models and human patients. 14,15 TGF-␤ binds specific serine/threonine kinase type I and type II receptors.…”

mentioning

confidence: 99%

Glucose-Induced TGF-β1 and TGF-β Receptor-1 Expression in Vascular Smooth Muscle Cells Is Mediated by Protein Kinase C-α

Lindschau

Quass²,

Menne³

et al. 2003

Hypertension

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Abstract-Sclerosis and increased matrix expression in diabetes are mediated by glucose-induced transforming growth factor (TGF)-␤1 expression. The intracellular effects of high glucose occur at least in part by way of protein kinase C (PKC). We previously described a role for PKC-␣ in glucose-induced permeability. We now investigated the hypothesis that glucose-induced expression of TGF-␤1 and its receptors (TGF-␤-R1 and -R2) are mediated by activation of this PKC isoform. TGF-␤1 and TGF-␤-R expressions were determined in vascular smooth muscle cells (VSMCs) by immunocytochemistry and Western blotting. PKC isoforms were assessed by confocal microscopy. PKC isoforms were inhibited with antisense oligodeoxynucleotides. PKC-␣ was upregulated by overexpression or microinjection. High glucose (20 mmol/L) increased VSMC TGF-␤1 and TGF-␤-R1 expression but not TGF-␤-R2 expression. PKC inhibitors and specific PKC-␣ downregulation by antisense treatment prevented this effect, whereas antisense treatment against PKC-␤, -⑀, and -had no influence. PKC-␣ overexpression increased TGF-␤1 and TGF-␤-R1 expression but not TGF-␤-R2 expression. PKC-␣ microinjection into individual VSMCs also increased TGF-␤1 and TGF-␤-R immunofluorescence. Last, VSMCs from PKC-␣-deficient mice did not respond to high glucose compared with VSMCs from wild-type mice. We propose that high glucose-induced TGF-␤1 and TGF-␤-R1 expression is mediated by PKC-␣. Our findings suggest an autocrine feedback mechanism and a possible role for PKC-␣ in diabetic vascular disease. Key Words: glucose Ⅲ growth substances Ⅲ protein kinases Ⅲ diabetes Ⅲ muscle, vascular, smooth Ⅲ atherosclerosis R enal hypertrophy, basement membrane thickening, and extracellular matrix accumulation characterize diabetic nephropathy. 1 Several cytokines with fibrogenic potential contribute to this, particularly transforming growth factor (TGF)-␤1. 2 TGF-␤1 increases matrix synthesis, inhibits matrix degradation, upregulates adhesion molecules, and enhances chemoattraction. 3,4 The possible importance of TGF-␤1 in diabetic nephropathy has been demonstrated in vitro by glucose-induced upregulation of this cytokine in different cell types. 5-13 Increased TGF-␤1 expression has also been demonstrated in diabetic animal models and human patients. 14,15 TGF-␤ binds specific serine/threonine kinase type I and type II receptors. The receptors form heteromeric cell surface complexes with TGF-␤. 16,17 The type II receptor determines ligand specificity, whereas the type I receptor interacts with the type II receptor and might not have a specific ligand. The type II receptor, likely in conjunction with the type I receptor, is probably required for the antiproliferative effect, whereas the type I receptor is the probable mediator of extracellular gene expression. 16,17 High glucose upregulates TGF-␤1 receptors in vitro and in vivo. 18,19 Hyperglycemia might mediate the effect of protein kinase C (PKC) activation. 20 -24 PKC consists of several isoforms with distinct cellular functions and different ex...

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Regulation of Glomerular Epithelial Cell Production of Fibronectin and Transforming Growth Factor-β by High Glucose, Not by Angiotensin II

Cited by 48 publications

References 0 publications

Cell Biology of the Glomerular Podocyte

Cell Biology of the Glomerular Podocyte

Urinary transforming growth factor-beta1 and alpha1-microglobulin in children and adolescents with type 1 diabetes.

Glucose-Induced TGF-β1 and TGF-β Receptor-1 Expression in Vascular Smooth Muscle Cells Is Mediated by Protein Kinase C-α

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