Glomerular Basement Membrane Antigens in Congenital and Acquired Nephrotic Syndrome in Childhood

Huttunen, Niilo‐Pekka; Hallman, N; Rapola, Juhani

doi:10.1159/000180664

Cited by 20 publications

(4 citation statements)

References 16 publications

(18 reference statements)

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“…In the chronic progressive glomerulosclerosis of mice transgenic for growth hormone (GH), glomerular hypertrophy induces slowly progressive podocyte failure (495). In all three diseases an increase in glomerular ILK mRNA is accompanied by the typical podocyte lesions of foot process effacement and denudation of the GBM (180,429,495). With the use of single podocyte RT-PCR (404) in combination with real-time RT-PCR, a significant increase of ILK mRNA was found in podocytes from proteinuric GH-transgenic mice compared with wild-type littermates, confirming podocyte-specific ILK induction.…”

Section: Integrin-linked Kinase In Podocyte Damagementioning

confidence: 99%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,322

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: Integrin-linked Kinase In Podocyte Damagementioning

confidence: 99%

Cell Biology of the Glomerular Podocyte

Pavenstädt

Kriz

Kretzler

2003

Physiological Reviews

1,322

1,278

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“…For experimental analysis, the third and most severe nephrosis, congenital nephrotic syndrome of the Finnish type (CNF), is an ideal human system to investigate gene expression alteration in proteinuria. CNF is a rare, recessively inherited disease with massive, treatment-resistant proteinuria already in utero but with no primary extrarenal manifestation (8). As an effective treatment protocol, bilateral nephrectomy, followed by renal transplantation, is performed.…”

mentioning

confidence: 99%

Integrin linked kinase as a candidate downstream effector in proteinuria

Kretzler¹,

Teixeira²,

Unschuld³

et al. 2001

FASEB j.

100

103

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The kidney glomerulus is responsible for the generation of a protein‐free ultrafiltrate. After injury, it shows a characteristic, uniform response leading to progressive renal failure. Recent studies of hereditary proteinuric diseases have revealed mutations in molecules involved in podocyte cell‐cell and cell‐matrix interaction. Associated cellular signaling events activated in proteinuria have not been analyzed so far. To identify proteinuria‐induced molecules, we used mRNA differential display in glomeruli from children with congenital nephrotic syndrome of the Finnish type. An increase in integrin linked kinase (ILK) mRNA, a β1‐integrin coupled serine threonine kinase, was identified. Observations suggest a role for ILK in glomerular failure. An up‐regulation of glomerular and Single‐podocyte ILK mRNA was found in two murine models of proteinuria. In cultured podocytes, integrin attachment to matrix inhibited ILK activity and podocyte damage with puromycin activated ILK. Stable overexpression of ILK in murine podocytes caused reduced matrix adhesion and led to considerable phenotype alteration compared with expression of a kinase‐defective ILK, paralleling aspects of in vivo podocyte damage. These results are consistent with ILK as a relevant player in the orchestration of podocyte matrix interaction and a candidate downstream regulator of podocyte permselectivity in glomerular diseases.

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“…In the chronic progressive glomerulosclerosis of mice transgenic for growth hormone (GH), glomerular hypertrophy induces slowly progressive podocyte failure (Wanke et al, 1993). In all three diseases an increase in glomerular ILK mRNA is found together with the typical podocyte lesions of foot process effacement and denudation of the GBM (Huttunen et al, 1976;Shirato et al, 1996a;Wanke et al, 1993). The alteration of the other glomerular cell types differs considerably between the evaluated diseases.…”

Section: Ilk Induction In Proteinuricmentioning

confidence: 99%

Regulation of adhesive interaction between podocytes and glomerular basement membrane

Kretzler¹

2002

Microscopy Res & Technique

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Glomerular filtration depends on well-orchestrated cell-cell and cell-matrix contacts of glomerular podocytes. Over the last years critical constituents of these contacts have been identified via molecular approaches. Podocyte cell-matrix interactions have been shown to be mediated in part by alpha(3)beta(1)-integrin heterodimers. Disturbances of integrin matrix interaction lead to detachment of podocytes in vitro, corresponding to the critical event of foot process retraction and glomerular basement membrane (GBM) denudation in vivo. Further, dystroglycan-mediated matrix attachment appears to play a critical role for podocyte foot process architecture. Downstream signaling events are currently elucidated concentrating mainly on integrin-dependent cascades and their consequences for podocyte adhesion and proliferation. An activation of the integrin-linked kinase in podocyte damage in vivo and in vitro makes this molecule a particularly interesting candidate for integrin-mediated inside-out and outside-in signaling in podocytes. Podocyte cell-cell interaction has been characterized in a few studies in vitro, indicating the slit diaphragm to be a modified adherens junction. The structural link between the cell-matrix and cell-cell contacts is maintained by the actin cytoskeleton, which may also enable cross-talk between these two cell contact sites. Examining podocyte function in tissue culture, animal models and human expression studies should allow further detailed dissection of the molecular pathways responsible for maintenance and failure of the glomerular filtration barrier.

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Glomerular Basement Membrane Antigens in Congenital and Acquired Nephrotic Syndrome in Childhood

Cited by 20 publications

References 16 publications

Cell Biology of the Glomerular Podocyte

Cell Biology of the Glomerular Podocyte

Integrin linked kinase as a candidate downstream effector in proteinuria

Regulation of adhesive interaction between podocytes and glomerular basement membrane

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