Biology subjects

Polzin, J.

Publications and source records attributed to Polzin, J..

4 recordsLinked to original sources

bioRxiv2026

The human GRK4Gamma griego minusculo 65L variant causes salt-sensitive hypertension by increasing renal SLC4A5 expression through the HDAC1 pathway

Salt-sensitive hypertension, a condition in which the blood pressure (BP) increases with an increase in salt intake, is influenced by behavioral, genetic, and environmental factors. Salt sensitivity is associated with variants of the G protein-coupled receptor kinase 4{gamma} (GRK4{gamma}) and the renal sodium bicarbonate cotransporter 2 (NBCe2), encoded by the solute carrier family 4 member 5 (SLC4A5). The R>65L variant (rs2960306) of human GRK4 (hGRK4{gamma} 65L) contributes to salt sensitivity through a signaling pathway and gene-gene interaction with SLC4A5. Global expression of GRK4{gamma} 65L in transgenic mice results in salt-sensitive hypertension, due in part to an increase in endogenous GRK4 and angiotensin type 1 receptor (AT1R) expression. Grk4 knockout (Grk4-/-) mice have decreased blood pressure and are salt-resistant. The expression of hGRK4{gamma} 65L only in the kidney of Grk4-/- mice increases BP in response to a high salt diet. The renal expression of SLC4A5 is increased in hGRK4{gamma} 65L transgenic mice, relative to mice expressing wild-type (WT) human GRK4 (hGRK4 65L), without endogenous mGrk4. Human renal proximal tubule cells (hRPTCs) endogenously expressing GRK4 WT and SLC4A5 WT, SLC4A5 variants, GRK4 65L, and both GRK4 65L and SLC4A5 variants were studied. SLC4A5 expression is increased in hRPTCs expressing GRK4 65L and in cells expressing both GRK4 65L and SLC4A5 variants compared with GRK4 WT and SLC4A5 WT. Luminal and basolateral sodium transport in hRPTCs is increased in the presence of both hGRK4 65L and SLC4A5 variants. GRK4 interacts with nuclear histone deacetylases (HDACs). Mice expressing hGRK4 65L only in the kidney have decreased expression but increased phosphorylation of HDAC1. HDAC1 expression is decreased and HDAC1 but not HDAC2 phosphorylation is increased in hRPTCs expressing both hGRK4 65L and SLC4A5 variants. The presence of hGRK4{gamma} 65L decreased HDAC1 expression but increased AT1R expression in the kidneys of mice on high salt diet. Our results show that GRK4{gamma} 65L causes salt-sensitive hypertension by increasing renal SLC4A5 and AT1R expressions by inhibiting the HDAC1 pathway.

molecular biology↗

bioRxiv2025

Role of NLRP3 activation in salt sensitive blood pressure regulation, effect of ND-13

Background and ObjectivesHigh salt intake is a major contributor to the development and exacerbation of hypertension, partly by inducing an inflammatory response through immune cell dysfunction. Inflammasomes, key components of the innate immune response, may influence blood pressure regulation. The renal DJ-1 protein is known for its antioxidant and anti-inflammatory properties. To explore novel pharmacological applications of renal DJ-1 pathway, we developed ND-13, a peptide consisting of 13 highly conserved amino acids derived from the DJ-1 sequence. In this study, we investigated the effects of ND-13 and MCC950, a specific NLRP3 inflammasome inhibitor, on blood pressure regulation in C57BL/6J mice on a high-salt diet. MethodsC57BL/6J mice were fed a high-salt diet (HS) for one week and then treated with ND-13 or MCC950, an NLRP3 inflammasome inhibitor. Subsequently, gene expression by qPCR, staining of immune cells, Sirius Red and Periodic Acid-Schiff (PAS) staining were determined in the mice kidneys, as well as the inflammasome activity in peritoneal cells. ResultsOne week of HS resulted increased in blood pressure, that was prevented by both ND-13 and MCC950 treatments. These treatments also prevented the increase in proteinuria that was accompanied by tubular protein deposits. Renal expression of inflammatory genes, immune cell infiltration, and renal collagen deposition were not observed in the HS group. Peritoneal macrophages isolated from HS treated mice exhibited enhanced IL-1{beta} release upon LPS+ATP stimulation, suggesting activation of the NLRP3 inflammasome. Treatment with ND-13 and MCC950 normalized this activity. Furthermore, ND-13 reduced IL-1{beta} mRNA expression in peritoneal macrophages. ConclusionsOur findings highlight the critical role of the NLRP3 inflammasome in salt-sensitive blood pressure regulation and suggest that ND-13 may serve as a potential therapeutic agent for preventing hypertension and associated inflammatory alterations induced by a high salt intake.

physiology↗

bioRxiv2019

Chemosymbiotic bivalves contribute to the nitrogen budget of seagrass ecosystems

In many seagrass sediments, lucinid bivalves and their sulfur-oxidizing symbionts are thought to underpin key ecosystem functions, but little is known about their role in nutrient cycles, particularly nitrogen. We used natural stable isotopes, elemental analyses, and stable isotope probing to study the ecological stoichiometry of a lucinid symbiosis in spring and fall. Chemoautotrophy appeared to dominate in fall, when chemoautotrophic carbon fixation rates were up to one order of magnitude higher as compared to the spring, suggesting a flexible nutritional mutualism. In fall, an isotope pool dilution experiment revealed carbon limitation of the symbiosis and ammonium excretion rates up to 10-fold higher compared to fluxes reported for non-symbiotic marine bivalves. These results provide evidence that lucinid bivalves can contribute substantial amounts of ammonium to the ecosystem. Given the preference of seagrasses for this nitrogen source, lucinid bivalves contribution may boost productivity of these important blue carbon ecosystems.

ecology↗

bioRxiv2017

BioSankey: Visualizing microbial communities and gene expression data over time

Metagenomics, RNA-seq, WGS (Whole Genome Sequencing) and other types of next-generation sequencing techniques provide quantitative measurements for single strains and genes over time. To obtain a global overview of the experiment and to explore the full potential of a given dataset, intuitive and interactive visualization tools are needed. Therefore, we established BioSankey, which allows to visualize microbial species in microbiome studies and gene expression over time as a Sankey diagram. These diagrams are embedded into a project-specific HTML page, that contains all information as provided during the installation process. BioSankey can be easily applied to analyse bacterial communities in time-series datasets. Furthermore, it can be used to analyse the fluctuations of differentially expressed genes (DEG). The output of BioSankey is a project-specific HTML page, which depends only on JavaScript to enable searches of interesting species or genes of interest without requiring a web server or connection to a database to exchange results among collaboration partners. BioSankey is a tool to visualize different data elements from single and dual RNA-seq datasets as well as from metagenomes studies.

bioinformatics↗