Biology subjects

Pluznick, J. L.

Publications and source records attributed to Pluznick, J. L..

3 recordsLinked to original sources

bioRxiv2022

Commensal Microbiota Regulate Renal Gene Expression

The gut microbiome impacts host gene expression not only in the colon, but also at distal sites including liver, white adipose tissue, and spleen. The gut microbiome also influences the kidney and is associated with renal diseases and pathologies; however, a role for the gut microbiome to modulate renal gene expression has not been examined. To determine if microbes modulate renal gene expression, we used whole-organ RNA sequencing (RNA-Seq) to compare gene expression in C57Bl/6 mice that are germ-free (lacking gut microbiota) versus conventionalized (with gut microbiota). 16S sequencing showed that males and females were similarly conventionalized, although Verrucomicrobia was higher in male mice. We find that renal gene expression is differentially regulated in the presence versus absence of microbiota, and that these changes are largely sex-specific. Although microbes also influence gene expression in the liver and large intestine, most differentially expressed genes (DEGs) in the kidney are not similarly regulated in the liver or large intestine. This demonstrates that the influence of the gut microbiota on gene expression is tissue specific. However, a minority of genes (n=4 in males, n=6 in females) were similarly regulated in all three tissues examined, including genes associated with circadian rhythm (Per1 in males and Per2 in females) and metal binding (Mt1 and Mt2 in both males and females). Finally, using a previously published single cell RNA-Seq (scRNA-Seq) dataset, we assigned a subset of DEGs to specific kidney cell types, revealing clustering of DEGs by cell type and/or sex. NEW & NOTEWORTHYIt is unknown whether the microbiome influences host gene expression in the kidney. Here, we utilize an unbiased, bulk RNA-Seq approach to compare gene expression in the kidneys of male and female mice with or without gut microbiota, as well as in liver and large intestine. This report demonstrates that renal gene expression is modulated by the microbiome in a sex- and tissue-specific manner.

physiology↗

bioRxiv2022

An evolutionarily conserved olfactory receptor is required for sex differences in blood pressure

Sex differences in blood pressure are well-established, with premenopausal women having lower blood pressure than men by [~]10mmHg; however, the underlying mechanisms are not fully understood. We report here that olfactory receptor 558 (Olfr558), which has not previously been studied in non-olfactory tissues, localizes to vascular smooth muscle cells in numerous tissues including the kidney and heart. In the kidney, Olfr558 colocalizes with renin (a hormone that plays a key role in blood pressure regulation) in the renal afferent arteriole. Based on the localization of Olfr558, we hypothesized that Olfr558 plays a role in blood pressure regulation. We find that sex differences in blood pressure are intact in Olfr558 wildtype (WT) mice, but, are absent in Olfr558 knockout (KO) mice. We find that male KO mice have lowered diastolic blood pressure, decreased renin expression and activity, and altered vascular reactivity. Female KO mice exhibit increased blood pressure and increased pulse wave velocity, indicating increased vascular stiffness. The human ortholog of Olfr558, OR51E1, was previously identified as a locus associated with diastolic blood pressure. We report here that a rare OR51E1 missense variant has a statistically significant sex interaction effect with diastolic blood pressure, increasing diastolic blood pressure in women but decreasing it in men. In addition, we characterize how two different clinically relevant OR51E1 variants influence OR51E1 signaling in vitro. In sum, our findings demonstrate an evolutionarily conserved role for Olfr558/OR51E1 to mediate sex differences in blood pressure by altering renin, vascular reactivity, and arterial stiffness.

physiology↗

bioRxiv2022

The Transcription Factor Foxi1 Promotes Expression of V-ATPase and Gpr116 in M-1 cells

The diverse functions of each nephron segment rely on the coordinated action of specialized cell populations that are uniquely defined by their transcriptional profile. In the collecting duct, there are two critical and distinct cell populations: principal cells and intercalated cells. Principal cells play key roles in the regulation of water, Na+, and K+, while intercalated cells are best known for their role in acid-base homeostasis. Currently, there are no in vitro systems that recapitulate the heterogeneity of the collecting ducts, which limits high-throughput and replicate investigations of genetic and physiological phenomena. Here, we have demonstrated that the transcription factor Foxi1 is sufficient to alter the transcriptional identity of M-1 cells, a murine cortical collecting duct cell line. Specifically, overexpression of Foxi1 induces the expression of intercalated cell transcripts including Gpr116, Atp6v1b1, Atp6v1g3, Atp6v0d2, Slc4a9, and Slc26a4. These data indicate that overexpression of Foxi1 differentiates M-1 cells towards a B-type intercalated cell phenotype and may provide a novel in vitro tool to study transcriptional regulation and physiological function of the renal collecting duct.

physiology↗