Biology subjects

Alencastre, I.

Publications and source records attributed to Alencastre, 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↗

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↗

bioRxiv2018

Osteoclasts control sensory neurons axonal growth through epidermal growth factor receptor signaling

The patterning of peripheral innervation is accomplished through the tissue expression, in specific space and timeframe, of attractive or repulsive axonal guidance cues. At the bone microenvironment, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, vascular endothelial growth factor, netrin-1 and others were described to regulate the nerve ingrowth towards the bone compartment, by acting directly on receptors expressed at the nerve terminals. Interestingly, besides the gradient of soluble factors, neurons were described to be responsive to extracellular vesicles (EV) derived from myelinating cells and mesenchymal stem cells. Here we provide evidence on a new mechanism by which peripheral innervation can be coordinated. We show that sensory nerves outgrowth and electric signal propagation are dependent on the EV secreted by osteoclasts, the bone resorbing cells. Furthermore, we demonstrate that the axonal sprouting is achieved through the activation of epidermal-growth factor receptor (EGFR) family signaling pathway. We proved that the EV-depleted osteoclast secretome leads to a significant decrease of neurons firing rate and axonal sprouting, concomitant with a decrease of EGFR/ErbB2 activation levels. Excitingly, the proteomic analysis of the osteoclast-derived EV cargo shows a high correlation with synaptic components reinforcing the role on sensory neurons/osteoclast crosstalk. Our findings that osteoclast-derived EV hold effect in axonal outgrowth, contributing actively to the dynamics of the sensory neurons sprouting and electrophysiology, is a step toward unraveling target mechanisms to control electrical signal propagation and nerve fibers sprouting and consequently open new avenues for the development of innovative therapies to control bone pain. Significance StatementSensory nerve fibers sprouting in bone pathologies is highly associated with pain. Thus, understanding the mechanisms behind sensory nerves ingrowth, sprouting and electrical activity, within the bone compartment, is essential for improving the strategies to overcome pain in bone disorders. We provide a new mechanism on the sensory nerves sprouting, indicating that the effect is dependent on the extracellular vesicles (EV) released by osteoclasts, through the epidermal growth factor receptor family targeting, by integrin independent pathways. We show different electrophysiology patterns being triggered in the presence of osteoclasts secretome and the abolishment of sensory neurons firing rate in EV-depleted conditions. Overall, our results elucidate novel mechanisms on the peripheral nerves sprouting, essential for pursuing new targets for bone pain therapies.

cell biology↗