Biology subjects

Brandao, I.

Publications and source records attributed to Brandao, I..

3 recordsLinked to original sources

bioRxiv2024

Peroxidasin expression is increased in intratumoural capillaries and in proximal tubular cells adjacent to clear cell renal cell carcinoma.

Peroxidasin (PXDN), is a heme peroxidase with a critical role in the crosslinking of type IV collagen, being essential for basement membrane integrity. In many cancers, PXDN overexpression has been linked with processes associated with poor disease outcomes, namely the impairment of endothelial functions, pathogenesis of vascular diseases, vascular remodelling, apoptosis, and tissue fibrosis. In RCC, almost nothing is so far known. In this work we characterized the expression of PXDN in tumour and non-neoplastic adjacent tissue from clear cell renal cell carcinoma (ccRCC) and renal oncocytoma by immunohistochemistry. Results showed a significant increase of PXDN expression in intratumoural capillaries of ccRCC in comparison with oncocytoma, and an increase in the proximal tubular epithelial cells of non-neoplastic adjacent parenchyma from ccRCC cases, in comparison with the same area from oncocytomas. Overall, our results suggest, for the first time, that PXDN may have a role in tumour angiogenesis that may favour metastases and tumour malignity, being also enrolled in the crosstalk between the tumour and adjacent tissue, that deserves further investigation. HighlightsO_LIPeroxidasin is increased in ccRCC microvasculature comparing to oncocytoma. C_LIO_LIPeroxidasin is increased in proximal tubules of ccRCC kidney adjacent parenchyma. C_LIO_LIIs Peroxidasin a modulator of tumour microenvironment promoting angiogenesis? C_LI

pathology↗

bioRxiv2024

Circulating microRNAs as biomarkers of chronic kidney disease and its association with renal and cardiovascular outcomes in non-dialysis patients

Chronic kidney disease (CKD) affects over 10% of the population worldwide and entails a significant risk for cardiovascular disease (CVD), leading to a 500-fold increase in cardiovascular mortality in advanced stages. Still, the pathophysiological mechanisms underlying kidney-heart intercommunication remain largely unknown. In recent years, microRNAs (miRNAs) emerged as important key regulators of gene expression that may serve as biomarkers for several diseases, however, their role in kidney-heart crosstalk in CKD remains underexplored. In this study, we evaluated the expression of a miRNA panel in plasma samples from non-dialysis CKD patients and explored their association with main comorbidities and significant outcomes in a 5-year follow-up. Results show that miR-30c-5p and miR-132-3p were downregulated in CKD patients presenting a significant power to discriminate the disease state. Importantly, only miR-30c-5p was downregulated in early glomerular filtration rate (GFR) categories, being able to discriminate these CKD patients from non-diseased individuals. Concerning cardiovascular outcomes, miR-199a-5p was found to be associated with an increased frequency of CVD. When analyzing the major disease outcomes in a 5-year time, miR-199a-5p upregulation at baseline was associated with increased mortality, while miR-324-3p was downregulated in patients who progressed to more advanced stages of the disease. These findings highlight the involvement of novel circulating miRNAs in CKD onset and progression, and identify, for the first time, the enrollment of miR-199a-5p in kidney-heart pathophysiological crosstalk, paving the way for the establishment of new biomarkers and therapeutic targets for CKD and its outcomes.

molecular biology↗

bioRxiv2023

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

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.

physiology↗