Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.12.21.572848

Characterization of peroxidasin expression in histologically normal human adult and fetal kidney tissue

Brandao, I.·Silva, R.·Conde, E.·Gomes, B.·Sampaio, P.·Costa Braga, A.·Reis Almeida, J.·Alencastre, I.·Oliveira, J. P.
View original source ↗Export metadata ↓

Abstract

Peroxidasin (PXDN) is an enzyme of the peroxidase family that plays a critical role in extracellular matrix (ECM) formation and tissue development. In the kidney, very few studies using animal cells suggested that PXDN may have a role in the maintenance of the structural and functional integrity of the renal ECM. Still, the normal expression and (patho)physiological roles of PDXN in the mature and developing human kidney remain unknown. In this work we used fluorescent immunohistochemistry and advanced microscopy and image processing methodologies to perform a quantitative characterization of PXDN expression in the different anatomic compartments of histologically normal kidney tissue, obtained from adult nephrectomy specimens, and from postmortem fetal and neonatal kidney specimens (excluding death by kidney disease and genitourinary developmental anomalies). Results show that PXDN is expressed in all mature kidney compartments, but at significantly higher levels in tubular epithelial cells, particularly in the distal tubules. A similar PXDN expression pattern was observed in the developing kidney, as early as the in the comma-shaped-body stage. In the fetal kidney, PXDN was diffusely expressed in the branches of the ureteric bud but not in the cells of the metanephric blastema. This is the first demonstration that PXDN is differentially expressed in histologically normal human renal parenchyma, exhibiting a remarkably consistent pattern of predominant tubular expression since the early stages of metanephrogenesis This data suggests a relevant, compartment-specific, role of PXDN in nephrogenesis and in the kidney physiology, highlighting a main role in tubular functions, that is worth further investigation.

Explore related subjects

physiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Brandao, I., Silva, R., Conde, E., Gomes, B., Sampaio, P., Costa Braga, A., Reis Almeida, J., Alencastre, I., Oliveira, J. P.. 2023-12-23. Characterization of peroxidasin expression in histologically normal human adult and fetal kidney tissue. https://doi.org/10.1101/2023.12.21.572848

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Hypothalamic Farnesoid X Receptor deficiency alters energy balance by modulating hepatic glucose production and adipose tissue metabolism through central insulin signaling.

Objectives: The bile acid nuclear receptor Farnesoid X Receptor (FXR, NR1H4) is a major regulator of metabolism and energy homeostasis in peripheral organs. It modulates bile acid, glucose, and lipid metabolism, as well as fat mass and body weight. However, FXR is also expressed in the brain, particularly in the hypothalamus, a key center for the regulation of energy homeostasis. Although one study has demonstrated a role for brain FXR activation in energy balance, its specific hypothalamic role is still unknown. Here, we examined the role of FXR in the mediobasal hypothalamus in the regulation of energy balance. Methods: We used a genetic approach combined with metabolic phenotyping to determine the effect of FXR invalidation in the mediobasal hypothalamus on metabolic parameters involved in the central regulation of energy homeostasis. Results: Our results demonstrate that hypothalamic FXR deficiency induces a positive energy balance, resulting in a reduction in energy expenditure due to alterations in glucose metabolism accompanied by structural changes in white adipose tissues. Conclusion: This study uncovers a previously unrecognized role for hypothalamic FXR in the central homeostatic control of energy balance, providing new insights into its contribution to peripheral glucose metabolism and adipose tissue structural remodeling.

physiology↗
bioRxiv2026

Rad and Phospholamban are Key Drivers of the Ventricular Adrenergic Response and Stress-Induced Arrhythmia

The adrenergic response is a fundamental mechanism that regulates heart rate (chronotropy), cardiac contractility (inotropy) and relaxation (lusitropy). Adrenergic stress is also a recognized trigger of arrhythmia in disease. Yet, our understanding of the underlying molecular basis remains incomplete. Protein kinase A (PKA) and the calcium/calmodulin-dependent kinase II (CaMKII) phosphorylate multiple targets proposed to participate in the adrenergic response, including the GTP-binding protein Rad, phospholamban (PLB) and ryanodine receptor 2 (RyR2). Here we demonstrate that phosphorylation of both Rad and PLB is necessary for inotropy and lusitropy. We show that changes in cardiac contractility and relaxation are primarily dependent on intracellular calcium handling. Finally, we report that Rad and PLB control stress-induced arrhythmogenesis, despite the phosphorylation of other pro-arrhythmic targets. We have identified the essential molecular components of the adrenergic response, resolving a long-standing debate in cardiac excitation-contraction coupling and refining current models of sympathetic regulation in health and disease.

physiology↗
bioRxiv2026

Light-cycle time-restricted feeding remodels a hidden layer of the cardiac transcriptome through sex-specific transcript switching

Light-cycle time-restricted feeding disrupts daily cardiovascular and thermoregulatory rhythms, but the molecular effects of light-cycle time-restricted feeding on the heart have been measured only at the level of total gene expression. We used Oxford Nanopore long-read RNA sequencing to resolve the full-length ventricular transcriptome from male and female mice under ad libitum feeding or light-cycle time-restricted feeding across the 24-hour cycle. Greater than 20% of cardiac transcripts represent unannotated variants of known genes absent from the current GENCODE reference annotation. Light-cycle time-restricted feeding reorganizes transcript usage across hundreds of genes, including genes encoding splicing regulators, largely without changing total gene expression. The genes affected are sex-specific, with fewer than 2% of changes shared at the gene, transcript, and transcript-usage levels. We show that transcript-level regulation is a previously underrecognized component of the cardiac response to altered feeding behavior, undetected by conventional short-read approaches.

physiology↗