Mo087plasmalemmal Vesicle-Associated Protein-1 (Plvap) Indicates the Formation of Diaphragm-Bridged Fenestrations of Glomerular Endothelial Cells in Kidney Disease

Tampe, Björn; Schridde, Laura; Hakroush, Samy

doi:10.1093/ndt/gfab078.0023

Cited by 3 publications

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“…GEN density, identified by nuclear staining for the ETS transcription factor ERG (36,37), was reduced in aged IgG2a control mice (443 ± 10 young vs. 290 ± 19 aged IgG2a control ERG + nuclei × 10 6 μm 3 , P < 0.0001), but was unchanged with aPD1ab (290 ± 19 aged IgG2a control vs. 287 ± 10 aged aPD1ab ERG + nuclei × 10 6 μm 3 , P = 0.902) (Supplemental Figure 2, A-D). Yet their age-dependent increase in the fenestral diaphragm protein plasmalemmal vesicle-associated protein-1 (PV-1), normally absent in healthy GENs and, when present, representing an immature and injured phenotype (38)(39)(40), was lowered by administration of aPD1ab (Supplemental Figure 2, E-G). Mesangial cell area, stained by Itga8 (α 8 integrin), was increased in aged IgG2a control mice compared with young mice, a trend that was also not changed by aPD1ab (Supplemental Figure 2, H-K).…”

Section: Resultsmentioning

confidence: 99%

Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease

Pippin¹,

Kaverina²,

Wang³

et al. 2022

Journal of Clinical Investigation

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With an aging population, kidney health becomes an important medical and socioeconomic factor. Kidney aging mechanisms are not well understood. We previously showed that podocytes isolated from aged mice exhibit increased expression of programmed cell death protein 1 (PD-1) surface receptor and its 2 ligands (PD-L1 and PD-L2). PDCD1 transcript increased with age in microdissected human glomeruli, which correlated with lower estimated glomerular filtration rate and higher segmental glomerulosclerosis and vascular arterial intima-to-lumen ratio. In vitro studies in podocytes demonstrated a critical role for PD-1 signaling in cell survival and in the induction of a senescence-associated secretory phenotype. To prove PD-1 signaling was critical to podocyte aging, aged mice were injected with anti–PD-1 antibody. Treatment significantly improved the aging phenotype in both kidney and liver. In the glomerulus, it increased the life span of podocytes, but not that of parietal epithelial, mesangial, or endothelial cells. Transcriptomic and immunohistochemistry studies demonstrated that anti–PD-1 antibody treatment improved the health span of podocytes. Administering the same anti–PD-1 antibody to young mice with experimental focal segmental glomerulosclerosis (FSGS) lowered proteinuria and improved podocyte number. These results suggest a critical contribution of increased PD-1 signaling toward both kidney and liver aging and in FSGS.

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Section: Resultsmentioning

confidence: 99%

Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease

Pippin¹,

Kaverina²,

Wang³

et al. 2022

Journal of Clinical Investigation

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Upregulated PD-1 Signaling is an Important Antagonist to Glomerular Health in Aged Kidneys

Pippin

Kaverina

Wang

et al. 2021

Preprint

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Kidney aging and its contribution to disease and its underlying mechanisms are not well understood. With an aging population, kidney health becomes an important medical and socioeconomic factor. We previously showed that podocytes isolated from aged mice exhibit increased expression of Programed Cell Death Protein 1 (PD-1) surface receptor and its two ligands (PD-L1, PD-L2). PDCD1 transcript increases with age in micro-dissected human glomeruli, which correlates with lower eGFR, and higher segmental glomerulosclerosis and vascular arterial intima to lumen ratio. In vitro studies in podocytes demonstrate a critical role for PD-1 signaling in cell survival and induction of a Senescence-Associated Secretory Phenotype (SASP). To prove PD-1 signaling is critical to podocyte aging, aged mice were injected with anti-PD-1 antibody (aPD-1ab). Treatment significantly improved the aging phenotype in both kidney and liver. In the glomerulus, it increased the life-span of podocytes, but not parietal epithelial, mesangial or endothelial cells. Transcriptomic and immunohistochemistry studies demonstrate that anti-PD-1 treatment improved the health-span of podocytes. It restored the expression of canonical podocyte genes, transcription factors and gene regulatory networks, increased cellular metabolism signatures and lessened SASPs. These results suggest a critical contribution for increased PD-1 signaling towards both kidney and liver aging.

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Fenestrated Endothelial Cells across Organs: Insights into Kidney Function and Disease

Mou,

Leeman,

Roye

et al. 2024

IJMS

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In the human body, the vascular system plays an indispensable role in maintaining homeostasis by supplying oxygen and nutrients to cells and organs and facilitating the removal of metabolic waste and toxins. Blood vessels—the key constituents of the vascular system—are composed of a layer of endothelial cells on their luminal surface. In most organs, tightly packed endothelial cells serve as a barrier separating blood and lymph from surrounding tissues. Intriguingly, endothelial cells in some tissues and organs (e.g., choroid plexus, liver sinusoids, small intestines, and kidney glomerulus) form transcellular pores called fenestrations that facilitate molecular and ionic transport across the vasculature and mediate immune responses through leukocyte transmigration. However, the development and unique functions of endothelial cell fenestrations across organs are yet to be fully uncovered. This review article provides an overview of fenestrated endothelial cells in multiple organs. We describe their development and organ-specific roles, with expanded discussions on their contributions to glomerular health and disease. We extend these discussions to highlight the dynamic changes in endothelial cell fenestrations in diabetic nephropathy, focal segmental glomerulosclerosis, Alport syndrome, and preeclampsia, and how these unique cellular features could be targeted for therapeutic development. Finally, we discuss emerging technologies for in vitro modeling of biological systems, and their relevance for advancing the current understanding of endothelial cell fenestrations in health and disease.

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Mo087plasmalemmal Vesicle-Associated Protein-1 (Plvap) Indicates the Formation of Diaphragm-Bridged Fenestrations of Glomerular Endothelial Cells in Kidney Disease

Cited by 3 publications

References 0 publications

Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease

Upregulated PD-1 signaling antagonizes glomerular health in aged kidneys and disease

Upregulated PD-1 Signaling is an Important Antagonist to Glomerular Health in Aged Kidneys

Fenestrated Endothelial Cells across Organs: Insights into Kidney Function and Disease

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