scholarly journals Progress in Pathogenesis of Proteinuria

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Aihua Zhang ◽  
Songming Huang
Keyword(s):  
Endothelial Cells ◽  
Glomerular Filtration ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Renal Diseases ◽  
Barrier Dysfunction ◽  
Glomerular Filtration Barrier ◽  
Glomerular Proteinuria ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells

Aims. Proteinuria not only is a sign of kidney damage, but also is involved in the progression of renal diseases as an independent pathologic factor. Clinically, glomerular proteinuria is most commonly observed, which relates to structural and functional anomalies in the glomerular filtration barrier. The aim of this paper was to describe the pathogenesis of glomerular proteinuria.Data Sources. Articles on glomerular proteinuria retrieved from Pubmed and MEDLINE in the recent 5 years were reviewed.Results. The new understanding of the roles of glomerular endothelial cells and the glomerular basement membrane (GBM) in the pathogenesis of glomerular proteinuria was gained. The close relationships of slit diaphragm (SD) molecules such as nephrin, podocin, CD2-associated protein (CD2AP), a-actinin-4, transient receptor potential cation channel 6 (TRPC6), Densin and membrane-associated guanylate kinase inverted 1 (MAGI-1),α3β1 integrin, WT1, phospholipase C epsilon-1 (PLCE1), Lmx1b, and MYH9, and mitochondrial disorders and circulating factors in the pathogenesis of glomerular proteinuria were also gradually discovered.Conclusion. Renal proteinuria is a manifestation of glomerular filtration barrier dysfunction. Not only glomerular endothelial cells and GBM, but also the glomerular podocytes and their SDs play an important role in the pathogenesis of glomerular proteinuria.

scholarly journals Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans

2016 ◽  
Vol 40 (5) ◽  
pp. 819-830 ◽  
Author(s):  
Janina Müller-Deile ◽  
Finn Gellrich ◽  
Heiko Schenk ◽  
Patricia Schroder ◽  
Jenny Nyström ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Glomerular Filtration ◽  
Cell Types ◽  
Endothelial Damage ◽  
Micro Rna ◽  
Glomerular Filtration Barrier ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells ◽  
Apoptotic Pathways

Background: TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. Methods: We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. Results: We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. Conclusion: Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins.

Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?

2018 ◽  
Vol 25 (13) ◽  
pp. 1525-1529 ◽  
Author(s):  
Joseph Fomusi Ndisang
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Glomerular Filtration ◽  
Glomerular Basement Membrane ◽  
Healthy Individuals ◽  
Kidney Dysfunction ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Glomerular Endothelial Cells ◽  
Fenestrated Endothelium

Background: Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes. Methods: A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures. Results and Conclusion: Generally, the onset of kidney dysfunction in many diabetic patients is characterized by albuminuria/proteinuria, a pathophysiological event triggered by several factors including; (i) endothelial activation and shading of glycocalyx, (ii) loss of endothelial cell function, (ii) re-uptake of albumin by podocyte through a scavenger receptors and (iv) rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement does not always lead to proteinuria, the dynamic interplay between all constituents of the glomerular filtration barrier including podocytes, endothelial cells and the basement membrane may be fundamental for the effective filtration in healthy individuals. Thus, a putative cross-talk amongst podocytes, endothelial cells and the basement membrane in the homeostasis of glomerular function is envisaged. Although, the exact nature of this cross-talk remains to be clearly elucidated, it is possible that the interaction between: (i) glomerular endothelial cells and podocytes, (ii) glomerular endothelial cells and glomerular basement membrane, (iii) podocytes and glomerular basement membrane, and (iv) the simultaneous interaction amongst the three components collectively underpin effective filtration in healthy individuals. A comprehensive understanding of these different interactions still remains elusive. The elucidation of these multifaceted interactions will set the stage for greater understanding of the pathophysiology of kidney dysfunction.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1815
Author(s):  
Jan Boeckhaus ◽  
Oliver Gross
Keyword(s):  
Glomerular Filtration ◽  
Alport Syndrome ◽  
Large Scale ◽  
Case Series ◽  
Hereditary Diseases ◽  
Glomerular Filtration Barrier ◽  
Early Effect ◽  
Filtration Barrier ◽  
First Case ◽  
Sodium Glucose Cotransporter

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.

scholarly journals Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cleo C. L. van Aanhold ◽  
Manon Bos ◽  
Katrina M. Mirabito Colafella ◽  
Marie-Louise P. van der Hoorn ◽  
Ron Wolterbeek ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Early Stage ◽  
Vascular Inflammation ◽  
Angiogenesis Inhibitor ◽  
Serum Levels ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
Soluble Thrombomodulin ◽  
Filtration Barrier ◽  
Glomerular Endothelium

AbstractThe endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.

scholarly journals Nck Proteins Maintain the Adult Glomerular Filtration Barrier

2009 ◽  
Vol 20 (7) ◽  
pp. 1533-1543 ◽  
Author(s):  
Nina Jones ◽  
Laura A. New ◽  
Megan A. Fortino ◽  
Vera Eremina ◽  
Julie Ruston ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier

Abstract 516: Knockdown of the Hypertension Associated Gene NOSTRIN Alters Glomerular Barrier Function in Zebrafish (Danio rerio)

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Torsten Kirsch ◽  
Jessica Kaufeld ◽  
Ron Korstanje ◽  
Dirk Hentschel ◽  
Hermann Haller ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Barrier Function ◽  
Morphological Changes ◽  
Glomerular Filtration Barrier ◽  
Cell Dysfunction ◽  
Larval Zebrafish ◽  
Filtration Barrier ◽  
Important Regulator ◽  
Glomerular Barrier ◽  
Prime Source

The bioavailability of nitric oxide (NO) has been associated with the development and progression of vascular and renal disease. NOSTRIN (for eNOS Traffic Inducer) has primarily been recognized as one important regulator of eNOS, the prime source of NO in the cardiovascular system, with a possible role in the pathogenesis of pre-eclampsia and the development of increased intrahepatic resistance in liver disease. Here, we identified NOSTRIN in the center of a QTL-overlap region in rat and human trait loci that are associated with hypertension. Glomerular NOSTRIN expression is detectable in podocytes in human and rat glomeruli and podocytic NOSTRIN expression is diminished in hypertensive kidney disease. We show that knockdown of NOSTRIN alters the glomerular filtration barrier function in larval zebrafish, inducing proteinuria and leading to ultrastructural morphological changes on the endothelial as well as epithelial side and the GBM of the glomerular capillary loop. We also demonstrate that NOSTRIN interacts with proteins associated with the podocyte slit membrane. We conclude that NOSTRIN expression is an important factor for the integrity of the glomerular filtration barrier. Disease related alteration of NOSTRIN expression may not only affect the vascular endothelium and therefore contribute to endothelial cell dysfunction but may also contribute to the development of podocyte disease and proteinuria.

Sign in / Sign up

Export Citation Format

Share Document