A5072573381- Renal Diseases and Glomerulopathies
- Sphingolipid Metabolism and Signaling
- Inflammasome and immune disorders
- Pancreatic function and diabetes
- Chronic Kidney Disease and Diabetes
- interferon and immune responses
- Cell Adhesion Molecules Research
- Systemic Lupus Erythematosus Research
- Platelet Disorders and Treatments
- Biomedical Research and Pathophysiology
- Cholesterol and Lipid Metabolism
- Ion Transport and Channel Regulation
- Diabetes Treatment and Management
- Lipid metabolism and disorders
- Lipid metabolism and biosynthesis
- Diverse Aspects of Tourism Research
- High Altitude and Hypoxia
- Receptor Mechanisms and Signaling
- Cardiovascular and Diving-Related Complications
- Genetic and Kidney Cyst Diseases
- RNA modifications and cancer
- Mathematical Biology Tumor Growth
- Cardiovascular Syncope and Autonomic Disorders
- Caveolin-1 and cellular processes
- Tuberous Sclerosis Complex Research
University of Miami
2013-2024
Immanuel Kant Baltic Federal University
2021-2023
Creative Commons
2023
University of Louisville
2023
University of Washington
2023
Oregon Health & Science University
2023
University of Miami Hospital
2022
Lomonosov Moscow State University
2020
Hypertension Institute
2016
Russian Academy of Sciences
2013
High levels of circulating TNF and its receptors, TNFR1 TNFR2, predict the progression diabetic kidney disease (DKD), but their contribution to organ damage in DKD remains largely unknown. Here, we investigated function local systemic podocyte injury. We cultured human podocytes with sera collected from patients, who displayed elevated levels, focal segmental glomerulosclerosis (FSGS) whose resembled those healthy patients. Exogenous administration or expression was equally sufficient cause...
Diabetic kidney disease (DKD) is the most common cause of ESRD in United States. Podocyte injury an important feature DKD that likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) a factor found elevated serum patients with FSGS and causes podocyte αVβ3 integrin-dependent migration vitro. Furthermore, integrin activation occurs association decreased podocyte-specific expression acid sphingomyelinase-like phosphodiesterase 3b...
Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. Suppression of ABCA1 expression occurs in glomeruli diabetic kidney (DKD) and human podocytes exposed to DKD sera collected prior the development DKD. We demonstrated that siRNA knockdown led reduced oxygen consumption capabilities associated alterations oxidative phosphorylation (OXPHOS)...
Abstract Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report SMPDL3b excess, as observed in podocytes diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival signaling by interfering with isoforms binding to caveolin-1 the PM. excess affects production of active sphingolipids resulting decreased ceramide-1-phosphate (C1P) content human vitro and cortexes db/db mice vivo....
Significance Statement A signaling molecule that plays a role in the innate immune system, stimulator of IFN genes (STING), is crucial regulator cyclic GMP-AMP synthase (cGAS)-STING pathway. This pathway regulates inflammation and energy homeostasis under conditions obesity, kidney fibrosis, AKI, but its exact pathogenesis glomerular diseases remains unclear. The authors found activation STING wild-type mice sufficient to cause albuminuria podocyte loss, cGAS-STING upregulated with...
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are anti-hyperglycemic agents that prevent glucose reabsorption in proximal tubular cells. SGLT2i improves renal outcomes both diabetic and non-diabetic patients, indicating it may have beneficial effects beyond glycemic control. Here, we demonstrate affects energy metabolism podocyte lipotoxicity experimental Alport syndrome (AS). In vitro, found the SGLT2 protein was expressed human mouse podocytes to a similar extent Newly established...
Abstract Impaired cellular cholesterol efflux is a key factor in the progression of renal, cardiovascular, and autoimmune diseases. Here we describe class 5-arylnicotinamide compounds, identified through phenotypic drug discovery, that upregulate ABCA1-dependent by targeting Oxysterol Binding Protein Like 7 (OSBPL7). OSBPL7 was as molecular target these compounds chemical biology approach, employing photoactivatable derivative cross-linking/immunoprecipitation assay. Further evaluation two...
The molecular mechanisms responsible for the development of proteinuria and glomerulosclerosis in radiation nephropathy remain largely unknown. Podocytes are increasingly recognized as key players pathogenesis primary secondary glomerular disorders. lipid-modulating enzyme sphingomyelin phosphodiesterase acid-like 3B (SMPDL3b) is a determinant podocyte injury known off target anti-CD20 antibody rituximab (RTX). current study investigates role sphingolipids radiation-induced podocytopathy....
BackgroundDiscoidin domain receptor 1 (DDR1) is a tyrosine kinase that activated by collagens involved in the pathogenesis of fibrotic disorders. Interestingly, de novo production collagen type I (Col I) has been observed Col4a3 knockout mice, mouse model Alport Syndrome (AS mice). Deletion DDR1 AS mice was shown to improve survival and renal function. However, mechanisms driving DDR1-dependent fibrosis remain largely unknown.MethodsPodocyte pDDR1 levels, Collagen cluster differentiation 36...
Lipotoxicity was recently reported in several forms of kidney disease, including focal segmental glomerulosclerosis (FSGS). Susceptibility to FSGS African Americans is associated with the presence genetic variants Apolipoprotein L1 gene (APOL1) named G1 and G2. If how endogenous APOL1 may alter mitochondrial function by modifying cellular lipid metabolism unknown. Using transgenic mice expressing (G0, or G2) under promoter, we show that risk variant expression does not impair at baseline....
Podocytes are a major component of the glomerular filtration barrier, and their ability to sense insulin is essential prevent proteinuria. Here we identify downstream effector GLUT4 as key modulator podocyte function in diabetic nephropathy (DN). Mice with podocyte-specific deletion (G4 KO) did not develop albuminuria despite having larger fewer podocytes than wild-type (WT) mice. Glomeruli from G4 KO mice were protected diabetes-induced hypertrophy, mesangial expansion, failed activate...
Sphingolipids have important functions as structural components of cells but they also function signaling molecules regulating different cellular processes such apoptosis, cell proliferation, migration, division and inflammation. Hence, a tight regulation the sphingolipid homeostasis is essential to maintain proper functions. Mammalian ORMDL proteins are orthologues yeast ORM1/2 proteins, which regulate ceramide synthesis in yeast. inhibit serine palmitoyltransferase (SPT), enzyme...
Abstract Background Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression treatment abatacept (a antagonist) has shown promise but remains controversial. Methods From 2012 2020, twelve patients developed post-KT range proteinuria, failed therapy, were treated abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults de novo...
The purpose of this study was to investigate the genetic mechanisms defense vascular reactions in response diving reflex humans with polymorphisms genes ADBR2, ACE, AGTR1, BDKRB2, and REN We hypothesized that protective reactions, reflex, are genetically determined distinguished gene renin-angiotensin kinin-bradykinin system. A total 80 subjects (19 ± 1.4 yr) participated study. intensity estimated using photoplethysmogram. I/D polymorphism (rs4340) ACE analyzed by PCR. (G/A, rs2368564),...
Microphysiological systems, also known as organs-on-chips, are microfluidic devices designed to model human physiology in vitro. Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due established microfabrication methods, and properties that make it suitable biological applications such low cytotoxicity, optical transparency, gas permeability. However, absorption of small molecules leaching uncrosslinked oligomers might hinder adoption PDMS-based drug discovery...