Glomerular basement membrane heparan sulfate in health and disease: A regulator of local complement activation

Borza, Dorin-Bogdan

doi:10.1016/j.matbio.2016.09.002

Cited by 42 publications

(40 citation statements)

References 111 publications

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“…By contrast, agrin had only 4.7% remaining 14 N in both fractions (Fig. 3C), consistent with its association with the lamina rara that is constantly renewed by the podocytes and endothelia 23,25,26 .…”

Section: Resultssupporting

confidence: 71%

Isotopic Nitrogen-15 Labeling of Mice Identified Long-lived Proteins of the Renal Basement Membranes

Liu

Xie

Jin

2020

Sci Rep

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The kidney is comprised of highly complex structures that rely on self-maintenance for their functions, and tissue repair and regeneration in renal diseases. We devised a proteomics assay to measure the turnover of individual proteins in mouse kidney. Mice were metabolically labeled with a specially formulated chow containing nitrogen-15 (15N) with the absence of normal 14N atoms. Newly synthesized proteins with 15N contents were distinguished from their 14N counterparts by mass spectrometry. In total, we identified over 4,000 proteins from the renal cortex with a majority of them contained only 15N. About 100 proteins had both 14N- and 15N-contents. Notably, the long-lived proteins that had large 14N/15N ratios were mostly matrix proteins. These included proteins such as type IV and type VI collagen, laminin, nidogen and perlecan/HSPG2 that constitute the axial core of the glomerular basement membrane (GBM). In contrast, the surface lamina rara proteins such as agrin and integrin had much shorter longevity, suggesting their faster regeneration cycle. The data illustrated matrix proteins that constitute the basement membranes in the renal cortex are constantly renewed in an ordered fashion. In perspective, the global profile of protein turnover is usefully in understanding the protein-basis of GBM maintenance and repair.

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Section: Resultssupporting

confidence: 71%

Isotopic Nitrogen-15 Labeling of Mice Identified Long-lived Proteins of the Renal Basement Membranes

Liu

Xie

Jin

2020

Sci Rep

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“…75 In total, 16 different combinations of these chains have been identified in mammals, for example, laminin α1β1γ1. 76 Laminins are a major constituent of the GBM, 77 mesangial ECM 58 and tubular basement membranes. 78 Similar to the change in the collagen IV network, there is a shift in laminin isoform expression during renal development in the GBM.…”

Section: Components Of the Renal Ecmmentioning

confidence: 99%

Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

Bülow

Boor

2019

J Histochem Cytochem.

277

187

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Kidney fibrosis is the common histological end-point of progressive, chronic kidney diseases (CKDs) regardless of the underlying etiology. The hallmark of renal fibrosis, similar to all other organs, is pathological deposition of extracellular matrix (ECM). Renal ECM is a complex network of collagens, elastin, and several glycoproteins and proteoglycans forming basal membranes and interstitial space. Several ECM functions beyond providing a scaffold and organ stability are being increasingly recognized, for example, in inflammation. ECM composition is determined by the function of each of the histological compartments of the kidney, that is, glomeruli, tubulo-interstitium, and vessels. Renal ECM is a dynamic structure undergoing remodeling, particularly during fibrosis. From a clinical perspective, ECM proteins are directly involved in several rare renal diseases and indirectly in CKD progression during renal fibrosis. ECM proteins could serve as specific non-invasive biomarkers of fibrosis and scaffolds in regenerative medicine. The gold standard and currently only specific means to measure renal fibrosis is renal biopsy, but new diagnostic approaches are appearing. Here, we discuss the localization, function, and remodeling of major renal ECM components in healthy and diseased, fibrotic kidneys and the potential use of ECM in diagnostics of renal fibrosis and in tissue engineering.

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“…Here it is primarily found as part of the proteoglycan, agrin [59,60]. Whether GBM HS plays a role in protein restriction is under debate [59,[61][62][63], although a general note for these and all Glx studies is that there is a need to discriminate between GAG of eGlx and elsewhere (i.e GBM, podocytes and mesangial cells).…”

Section: Glomerular Eglxmentioning

confidence: 99%

Endothelial glycocalyx restoration by growth factors in diabetic nephropathy

Desideri

Onions

Baker

et al. 2019

BIR

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The endothelial glycocalyx (eGlx) constitutes the first barrier to protein in all blood vessels. This is particularly noteworthy in the renal glomerulus, an ultrafiltration barrier. Leakage of protein, such as albumin, across glomerular capillaries results in albumin in the urine (albuminuria). This is a hall mark of kidney disease and can reflect loss of blood vessel integrity in microvascular beds elsewhere. We discuss evidence demonstrating that targeted damage to the glomerular eGlx results in increased glomerular albumin permeability. EGlx is lost in diabetes and experimental models demonstrate loss from glomerular endothelial cells. Vascular endothelial growth factor (VEGF)A is upregulated in early diabetes, which is associated with albuminuria. Treatment with paracrine growth factors such as VEGFC, VEGF165b and angiopoietin-1 can modify VEGFA signalling, rescue albumin permeability and restore glomerular eGlx in models of diabetes. Manipulation of VEGF receptor 2 signalling, or a common eGlx biosynthesis pathway by these growth factors, may protect and restore the eGlx layer. This would help to direct future therapeutics in diabetic nephropathy.

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Glomerular basement membrane heparan sulfate in health and disease: A regulator of local complement activation

Cited by 42 publications

References 111 publications

Isotopic Nitrogen-15 Labeling of Mice Identified Long-lived Proteins of the Renal Basement Membranes

Isotopic Nitrogen-15 Labeling of Mice Identified Long-lived Proteins of the Renal Basement Membranes

Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

Endothelial glycocalyx restoration by growth factors in diabetic nephropathy

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