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Lipid biology of the podocyte--new perspectives offer new opportunities.

ABSTRACT: In the past 15 years, major advances have been made in understanding the role of lipids in podocyte biology. First, susceptibility to focal segmental glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1 sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an important component of HDL. Second, acid sphingomyelinase-like phosphodiesterase 3b encoded by SMPDL3b has a role in the conversion of sphingomyelin to ceramide and its levels are reduced in renal biopsy samples from patients with recurrent FSGS. Furthermore, decreased SMPDL3b expression is associated with increased susceptibility of podocytes to injury after exposure to sera from these patients. Third, in many individuals with membranous nephropathy, autoantibodies against the phospholipase A2 (PLA2) receptor, which is expressed in podocytes, have been identified. Whether these autoantibodies affect the activity of PLA2, which liberates arachidonic acid from glycerophospholipids and modulates podocyte function, is unknown. Fourth, clinical and experimental evidence support a role for ATP-binding cassette sub-family A member 1-dependent cholesterol efflux, free fatty acids and glycerophospolipids in the pathogenesis of diabetic kidney disease. An improved understanding of lipid biology in podocytes might provide insights to develop therapeutic targets for primary and secondary glomerulopathies.

SUBMITTER: Fornoni A

PROVIDER: S-EPMC4386893 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Lipid biology of the podocyte--new perspectives offer new opportunities.

Fornoni Alessia A Merscher Sandra S Kopp Jeffrey B JB

Nature reviews. Nephrology 20140527 7

In the past 15 years, major advances have been made in understanding the role of lipids in podocyte biology. First, susceptibility to focal segmental glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1 sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an important component of HDL. Second, acid sphingomyelinase-like phosphodiesterase 3b encoded by SMPDL3b has a role in the conversion of sphingomyelin to ceramide and its levels are reduced in rena ...[more]

PMID: 24861084

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Project description:BackgroundThe prevalence of diabetes mellitus (DM) is increasing rapidly worldwide. Simultaneously, technological advances are offering new opportunities for better management of type 1 diabetes mellitus (T1DM). Telemetry, the remote acquisition of patient data via a telecommunication system, is a promising field of application in eHealth and is rapidly gaining importance.ObjectiveThe aim of this study was to summarize the current evidences available on the effectiveness of telemetric approaches in T1DM management. This systematic meta-review examined different types of interventions of the technologies used in communication between health care professionals and patients as well as the key outcomes.MethodsWe performed a systematic search in Web of Science Core Collection, EMBASE, Cochrane Library, MEDLINE via PubMed, and CINAHL databases in April 2020 with regard to the effectiveness of telemetric interventions for T1DM. We classified the interventions into 4 categories according to the technology used: (1) real-time video communication, (2) real-time audio communication, (3) asynchronous communication, and (4) combined forms of communication (real-time and asynchronous). We considered various study designs such as systematic reviews, clinical trials, meta-analyses, and randomized controlled trials and focused on the key outcomes. Additionally, a funnel plot based on hemoglobin A1c (HbA1c) values and different quality assessments were performed.ResultsWe identified 17 (6 high quality and 9 moderate quality) eligible publications: randomized controlled trials (n=9), systematic reviews and meta-analyses (n=5), cohort studies (n=2), and qualitative publications (n=1). Of 12 studies, 8 (67%) indicated a (significant or nonsignificant) reduction in HbA1c levels; 65% (11/17) of the studies reported overall (mildly) positive effects of telemetric interventions by addressing all the measured outcomes. Asynchronous interventions were the most successful for patients diagnosed with T1DM, but no technology was clearly superior. However, there were many nonsignificant results and not sustained effects, and in some studies, the control group benefited from telemetric support or increased frequency of contacts.ConclusionsBased on the currently available literature, this systematic meta-review shows that telemetric interventions cause significant reduction in HbA1c levels and result in overall positive effects in T1DM management. However, more specified effects of telemetric approaches in T1DM management should be analyzed in detail in larger cohorts.

Project description:BACKGROUND:Although telomerase has potential for age-related disease intervention, the overexpression of telomerase in about 90% of cancers, and in HIV virus reservoirs, cautions against se in anti-aging telomerase therapeutics. While multiple reviews document the canonical function of telomerase for maintenance of telomeres, as well as an increasing numbers of reviews that reveal new non-canonical functions of telomerase, there was no systematic review that focuses on the array of associates of the subunit of Telomerase Reverse transcriptase protein (TERT) as pieces of the puzzle to assemble a picture of the how specific TERT complexes uniquely impact aging and age-related diseases and more can be expected. METHODS:A structured search of bibliographic data on TERT complexes was undertaken using databases from the National Center for Biotechnology Information Pubmed with extensive access to biomedical and genomic information in order to obtain a unique documented and cited overview of TERT complexes that may uniquely impact aging and age-related diseases. RESULTS:The TERT associations include proper folding, intracellular TERT transport, metabolism, mitochondrial ROS (Reactive Oxygen Species) regulation, inflammation, cell division, cell death, and gene expression, in addition to the well-known telomere maintenance. While increase of cell cycle inhibitors promote aging, in cancer, the cell cycle check-point regulators are ambushed in favor of cell proliferation, while cytoplasmic TERT protects a cell cycle inhibitor in oxidative stress. The oncogene cMyc regulates gene expression for overexpression of TERT, and reduction of cell cycle inhibitors-the perfect storm for cancer promotion. TERT binds with the oncogene RMRP RNA, and TERT-RMRP function can regulate levels of that oncogene RNA, and TERT in a TBN complex can regulate heterochromatin. Telomerase benefit and novel function in neurology and cardiology studies open new anti- aging hope. GV1001, a 16 amino acid peptide of TERT that associates with Heat Shock Proteins (HSP's), bypasses the cell membrane with remarkable anti disease potential. CONCLUSIONS:TERT "associates" are anti-cancer targets for downregulation, but upregulation in antiaging therapy. The overview revealed that unique TERT associations that impact all seven pillars of aging identified by the Trans-NIH Geroscience Initiative that influence aging and urge research for appropriate targeted telomerase supplements/ stimulation, and inclusion in National Institute on Aging Intervention Testing Program. The preference for use of available "smart drugs", targeted to only cancer, not off-target anti- aging telomerase is implied by the multiplicity of TERT associates functions.

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Lipid biology of the podocyte--new perspectives offer new opportunities.

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Lipid biology of the podocyte--new perspectives offer new opportunities.

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