A5066442908- Skin and Cellular Biology Research
- Ion Transport and Channel Regulation
- Diet and metabolism studies
- Olfactory and Sensory Function Studies
- Electrolyte and hormonal disorders
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
- Gut microbiota and health
- Plant Reproductive Biology
- Cellular Mechanics and Interactions
- Microtubule and mitosis dynamics
- Dermatological and Skeletal Disorders
- Birth, Development, and Health
- Renal and related cancers
- Heart Rate Variability and Autonomic Control
- Vagus Nerve Stimulation Research
- Clostridium difficile and Clostridium perfringens research
- Respiratory Support and Mechanisms
- Cutaneous lymphoproliferative disorders research
- Protein Structure and Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Nuclear Structure and Function
- Cardiac Health and Mental Health
- Genetic and Kidney Cyst Diseases
- Dietary Effects on Health
National Heart Lung and Blood Institute
2021-2024
National Institutes of Health
2021-2024
Johns Hopkins Medicine
2016-2021
Johns Hopkins University
2015-2021
University of Padua
2021
University of Alabama at Birmingham
2021
Short-chain fatty acids (SCFAs) are metabolites produced almost exclusively by the gut microbiota and an essential mechanism which microbes influence host physiology. Given that SCFAs induce vasodilation, we hypothesized they might have additional cardiovascular effects. In this study, novel mechanisms of SCFA action were uncovered examining acute effects on physiology in vivo ex vivo. Acute delivery conscious radiotelemetry-implanted mice results a simultaneous decrease both mean arterial...
Abstract Background Protein phosphorylation is one of the most prevalent posttranslational modifications involved in molecular control cellular processes, and mediated by over 520 protein kinases humans other mammals. Identification responsible for events key to understanding signaling pathways. Unbiased phosphoproteomics experiments have generated a wealth data that can be used identify kinase targets their preferred substrate sequences. Methods This study utilized prior from mass...
Short-chain fatty acids (SCFAs) are fermentation by-products of gut microbes which have been linked to positive effects on host physiology; the most abundant SCFA is acetate. Exogenous administration acetate alters metabolism, immune function, and blood pressure, making it a biologic interest. The attributed activation G-protein–coupled receptors other proteins (i.e., HDACs), often occurring at locations distant from such as pancreas or kidney. However, due technical difficulties costs,...
The type I intermediate filament keratin 16 (KRT16 gene; K16 protein) is constitutively expressed in ectoderm-derived appendages and palmar/plantar epidermis robustly induced when the experiences chemical, mechanical or environmental stress. Missense mutations at KRT16 locus can cause pachyonychia congenita (PC, OMIM:167200) focal non-epidermolytic palmoplantar keratoderma (FNEPPK, OMIM:613000), which each entail painful calluses on palmar plantar skin. Krt16-null mice develop footpad...
ABSTRACT Keratin 17 (KRT17; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte lines lacking K17 exhibit flatter nuclei relative normal. Re-expression of wild-type K17, but not mutant form an intact localization signal (NLS), rescues morphology KRT17-null cells. Analyses primary cultures skin keratinocytes from...
Olfactory receptor 78 (Olfr78) is a G protein-coupled (GPCR) that expressed in the juxtaglomerular apparatus (JGA) of kidney as well peripheral vasculature, and activated by gut microbial metabolites. We previously reported Olfr78 plays role renin secretion isolated glomeruli, knockout (KO) mice have lower plasma activity. also noted anesthetized mice, Olfr78KO appeared to be hypotensive. In this study, we used radiotelemetry determine chronic blood pressure regulation. found not...
Kidney transport and other renal functions are regulated by multiple G protein-coupled receptors (GPCRs) expressed along the tubule. The rapid, recent appearance of comprehensive unbiased gene expression data in various tubule segments, chiefly RNA sequencing protein mass spectrometry data, has provided a means identifying patterns GPCR To allow for mapping, we first curated list GPCRs genomes mice, rats, humans (https://hpcwebapps.cit.nih.gov/ESBL/Database/GPCRs/) using online sources. We...
Vasopressin regulates renal water excretion through control of the aquaporin-2 channel in collecting duct cells. Studies vasopressin-induced protein phosphorylation have focused mainly on aquaporin-2. This study describes 44 phosphoproteins other than that undergo vasopressin-mediated changes and summarizes potential physiological roles each.
Recent studies by our laboratory and others have highlighted the important role played short chain fatty acids (SCFA) produced gut microbiota their effect on host physiology. Acetate, most abundant SCFA present in blood, has been shown to modulate blood pressure control through at least two mechanisms; renin release juxtaglomerular apparatus, changes vascular tone peripheral resistance beds (Pluznick, Protzko et al. 2013). Prior that intravenous administration of SCFAs causes acute...
Abstract Keratin 17 ( KRT17 ; K17), a non-lamin intermediate filament protein, was recently found to occur in the nucleus. We report here on K17-dependent differences nuclear morphology, chromatin organization, and cell proliferation. Human tumor keratinocyte lines lacking K17 exhibit flatter nuclei relative normal. Re-expression of wildtype K17, but not mutant form an intact localization signal (NLS), rescues morphology null cells. Analyses primary cultures skin keratinocytes from mouse...
Ureteral obstruction is marked by disappearance of the vasopressin-dependent water channel aquaporin-2 (AQP2) in renal collecting duct and polyuria upon reversal. Most studies unilateral ureteral (UUO) models have examined late time points, obscuring early signals that trigger loss AQP2.We performed RNA-Seq on microdissected rat cortical ducts (CCDs) to identify signaling pathways after establishment UUO.Vasopressin V2 receptor (AVPR2) mRNA was decreased 3 hours UUO, identifying one cause...
Circadian variability in kidney function is well recognized but often ignored as a potential confounding variable physiological experiments. Here, we have created data resource consisting of expression levels for mRNA transcripts microdissected proximal tubule segments from mice the time day. Small-sample RNA sequencing was applied to S1 convoluted tubules and S2 straight tubules. After stringent filtering, were analyzed using JTK-Cycle detect periodicity. The set provided user-friendly...
Recent studies by our laboratory have identified Olfactory Receptor 78 (Olfr78) as a short chain fatty acid (SCFA) receptor which modulates blood pressure. We previously reported that in ex vivo preparations of glomeruli, Olfr78 responds to SCFA's such propionate mediate renin release the juxtaglomerular apparatus (JGA) kidney. Similarly, whole‐animal KO mice lowered plasma levels, and are hypotensive.(Pluznick, Protzko et al. 2013). While it is known G‐protein coupled receptor, precise...
Metabolites produced by the gut microbiota can affect host physiology; one class of these metabolites are short chain fatty acids (SCFAs). Prior work our laboratory has shown that intravenous administration SCFAs causes acute hypotension (Pluznick, Protzko et al. 2013) and treating vessels with ex vivo results in vasorelaxation (Natarajan, Hori 2016). To expand upon findings, we performed IP injections acetate mice were implanted DSI telemetry transmitters to monitor mean arterial pressure...
The microbiome has been implicated in blood pressure regulation and recent studies have found that gut‐derived microbial short chain fatty acids (SCFAs) modulate pressure. This is mediated, at least part, by Olfactory receptor 78 (Olfr78), a G‐protein coupled (GPCR) which responds to SCFAs renin release. Other renal GPCRs respond include Olfr558, Gpr41, Gpr43. Although we previously studied the physiology of Olfr78 null mice, do not know whether expression other SCFA receptors, or key genes,...
ABSTRACT Circadian variability in kidney function has long been recognized but is often ignored as a potential confounding variable vivo physiological experiments. To provide guide for studies on the proximal tubule, we have now created data resource consisting of expression levels all measurable mRNA transcripts microdissected tubule segments from mice time day. This approach employs small-sample RNA-sequencing (RNA-seq) applied to renal tubules including both S1 convoluted (PCTs) and S2...
Kidney transport and other renal functions are regulated by multiple G-protein coupled receptors (GPCRs) expressed along the tubule. Development of unbiased ‘-omics’ approaches next-generation sequencing (NGS)-based techniques, including transcriptomics in microdissected tubules, single-cell transcriptomics, proteomics tubules have provided a means identifying patterns GPCR expression. To allow for complete mapping, we first curated comprehensive list GPCRs genomes rats, mice humans...