Principles of Zebrafish Nephron Segment Development

Journal of Developmental Biology, Journal Year: 2023, Volume and Issue: 11(1), P. 14 - 14

Published: March 18, 2023

Nephrons are the functional units which comprise kidney. Each nephron contains a number of physiologically unique populations specialized epithelial cells that organized into discrete domains known as segments. The principles segment development have been subject many studies in recent years. Understanding mechanisms nephrogenesis has enormous potential to expand our knowledge about basis congenital anomalies kidney and urinary tract (CAKUT), contribute ongoing regenerative medicine efforts aimed at identifying renal repair generating replacement tissue. study zebrafish embryonic kidney, or pronephros, provides opportunities identify genes signaling pathways control development. Here, we describe advances patterning differentiation zebrafish, with focus on distal formation.

Language: Английский

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Podocytopathy in the mesangial proliferative immunoglobulin A nephropathy: new insights into the mechanisms of damage and progression

Nephrology Dialysis Transplantation, Journal Year: 2018, Volume and Issue: 34(8), P. 1280 - 1285

Published: Dec. 21, 2018

Immunoglobulin A nephropathy (IgAN) was defined as a mesangiopathic disease, since the primary site of deposition IgA immune material is mesangium, and proliferation mesangial cells matrix excess are first histopathologic lesions. However, relentless silent progression IgAN mostly due to development persistent proteinuria, recent studies indicate that major role played by previous damage function anatomy podocytes. In IgAN, podocytopathic changes consequence initial alterations in area with accumulation containing material. Podocytes therefore affected interactions messages originally driven from mesangium. After continuous insult, podocytes detach glomerular basement membrane. This podocytopathy favours not only focal segmental sclerosis, but also progressive renal loss. It still debated whether these lesions can be prevented or cured corticosteroid/immunosuppressive treatment. We aimed review data on mechanisms implicated present showing new molecular risk factors for this disease. Moreover, observations may target drugs focused decreasing activity inflammatory reactions improving podocyte survival.

Language: Английский

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Endoplasmic reticulum–associated degradation is required for nephrin maturation and kidney glomerular filtration function

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(7)

Published: Feb. 28, 2021

Podocytes are key to the glomerular filtration barrier by forming a slit diaphragm between interdigitating foot processes; however, molecular details and functional importance of protein folding degradation in ER remain unknown. Here, we show that SEL1L-HRD1 complex ER-associated (ERAD) is required for formation function. ERAD highly expressed podocytes both mouse human kidneys. Mice with podocyte-specific Sel1L deficiency develop podocytopathy severe congenital nephrotic syndrome an impaired shortly after weaning die prematurely, median lifespan approximately 3 months. We mechanistically nephrin, type 1 membrane causally linked syndrome, endogenous substrate. attenuated maturation nascent leading its retention ER. also various autosomal-recessive nephrin disease mutants were unstable broken down ERAD, which pathogenicity toward WT allele. This study uncovers critical role function provides insights into pathogenesis associated mutants.

Language: Английский

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Extracellular Vesicles Derived from Endothelial Progenitor Cells Protect Human Glomerular Endothelial Cells and Podocytes from Complement- and Cytokine-Mediated Injury

Cells, Journal Year: 2021, Volume and Issue: 10(7), P. 1675 - 1675

Published: July 2, 2021

Glomerulonephritis are renal inflammatory processes characterized by increased permeability of the Glomerular Filtration Barrier (GFB) with consequent hematuria and proteinuria. endothelial cells (GEC) podocytes part GFB contribute to maintenance its structural functional integrity through release paracrine mediators. Activation complement cascade pro-inflammatory cytokines (CK) such as Tumor Necrosis Factor α (TNF-α) Interleukin-6 (IL-6) can alter function, causing acute glomerular injury progression toward chronic kidney disease. Endothelial Progenitor Cells (EPC) bone-marrow-derived hematopoietic stem circulating in peripheral blood able induce angiogenesis repair injured endothelium releasing mediators including Extracellular Vesicles (EVs), microparticles involved intercellular communication transferring proteins, lipids, genetic material (mRNA, microRNA, lncRNA) target cells. We have previously demonstrated that EPC-derived EVs activate an angiogenic program quiescent renoprotection different experimental models. The aim present study was evaluate vitro protective effect on GECs cultured detrimental conditions CKs (TNF-α/IL-6) protein C5a. were internalized both mainly a L-selectin-based mechanism. In GECs, enhanced formation capillary-like structures cell migration modulating gene expression inducing growth factors VEGF-A HGF. presence CKs, C5a, protected from apoptosis decreasing oxidative stress prevented leukocyte adhesion inhibiting molecules (ICAM-1, VCAM-1, E-selectin). On podocytes, inhibited nephrin shedding induced co-culture model GECs/podocytes mimicked GFB, function permeselectivity inflammatory-mediated damage. Moreover, RNase pre-treatment abrogated their effects, suggesting crucial role RNA transfer damaged conclusion, preserved complement- cytokine-induced damage, potential therapeutic agents for drug-resistant glomerulonephritis.

Language: Английский

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Research progress on the treatment of diabetic nephropathy with leech and its active ingredients

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 26, 2024

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and common cause chronic kidney disease. There currently lack effective treatments for DN, the prognosis patients remains poor. Hirudin, one primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, anti-inflammatory properties, exhibiting significant protective effects on kidneys. In recent years, there has been surge interest in studying potential benefits hirudin, especially its role management DN. This article delves into mechanisms by which hirudin contributes to treatment DN clinical efficacy.

Language: Английский

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