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Proteinuria: Basic Mechanisms, Pathophysiology and Clinical Relevance pp 11–21Cite as

Glomerular Mechanisms of Proteinuria

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Abstract

The glomerular filtration barrier (GFB) consisting of glomerular endothelial cells, the glomerular basement membrane and podocytes is the key structure within the nephron that prevents filtration of serum proteins into the urine. While all three components are necessary for the development and maintenance of the GFB, the majority of investigations have focused on the role of the podocyte in preventing proteinuria. Podocytes are terminally differentiated cells with a highly complex architecture. Mutations in structural or signaling proteins in podocytes lead to proteinuria, as does podocyte damage leading to alterations in podocyte shape or progressive podocyte loss. Podocytes are not only important structural elements within the GFB but also play an active role in handling serum proteins such as albumin and IgG. Advanced imaging methods have further contributed to our understanding of the glomerular regulation of protein filtration in normal and disease states.

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Abbreviations

ACTN4:

Actinin alpha 4

Angpt:

Angiopoietin

APOL1:

Apolipoprotein L1

COX2:

Cyclooxygenase 2

CXCL12:

1/C-X-C chemokine ligand 12

CXCR4:

C-X-C chemokine receptor 4

ESRD:

End stage renal disease

FSGS:

Focal segmental glomerulosclerosis

GAGs:

Glycosaminoglycans

GBM:

Glomerular basement membrane

GEC:

Glomerular endothelial cells

GFB:

Glomerular filtration barrier

Grb2:

Growth-factor receptor binder 2

GSC:

Glomerular sieving coefficient

GTP:

Guanosine-5′-triphosphate

IgG:

Immunoglobulin

L:

Liter

LAMB2:

Lamininβ2

NcK:

Non catalytic kinase

nm:

Nanometer

NPHS1:

Gene that encodes nephrin

NPHS2:

Gene that encodes podocin

N-WASP:

Wiskott–Aldrich syndrome protein

PEC:

Parietal epithelial cells

PI3k:

p85/phosphatidylinositol 3-kinase

PLCg:

Phospholipase C gamma

SH2/3:

Src homology 2 (SH2)/Src homology 3 (SH3)

TAK1:

Transforming growth factor (TGF)-β activated kinase 1

Tie:

Tyrosine-protein kinase receptor

TRPC6:

Transient receptor potential cation channel subfamily 6

VEGFA:

Vascular endothelial growth factor a

VEGFR:

VEGF receptor

WT1:

Wilms tumor protein 1

ZO-1:

Zonula occludens-1

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  1. Division of Renal Diseases and Hypertension, University of Colorado Denver, 12700, E 19th Avenue, C281, Aurora, CO, 80045, USA

    Evgenia Dobrinskikh & Judith Blaine

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  1. Evgenia Dobrinskikh
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  1. Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado, USA

    Judith Blaine

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Dobrinskikh, E., Blaine, J. (2016). Glomerular Mechanisms of Proteinuria. In: Blaine, J. (eds) Proteinuria: Basic Mechanisms, Pathophysiology and Clinical Relevance. Springer, Cham. https://doi.org/10.1007/978-3-319-43359-2_2

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