2,296 research outputs found
Editorial: Repair and regenerative mechanisms by stem/progenitor cells and secretome: The golden twenties of translational medicine
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The Heterogeneity of Renal Stem Cells and Their Interaction with Bio- and Nano-materials
No full textFor a long time, the kidney has been considered incapable of regeneration. Instead, in recent years, studies have supported the existence of heterogeneity of renal stem/progenitor cells with the ability to regenerate both glomerular and tubular epithelial cells. Indeed, several studies evidence that renal progenitor cells, releasing chemokines, growth factors, microvesicles, and transcription factors through paracrine mechanisms, can induce tissue regeneration and block pathological processes of the kidney. In this chapter the potentiality of the kidney regenerative processes is considered and reviewed, and the main classes of stem/progenitor cells that might contribute to the renal tissue renewal is analyzed. Moreover, we evaluate the role of biomaterials in the regulation of cellular functions, specifically addressing renal stem/progenitor cells. Materials can be synthesized and tailored in order to recreate a finely structured microenvironment (by nanostructures, nanofibers, bioactive compounds, etc.) with which the cells can interact actively. For instance, by patterning substrates in regions that alternately promote or prevent protein adsorption, cell adhesion and spreading processes can be controlled in space. We illustrate the potentiality of nanotechnologies and engineered biomaterials in affecting and enhancing the behavior of renal stem/progenitor cells. Although there are still many challenges for the translation of novel therapeutics, advances in biomaterials and nanomedicine have the potential to drastically change the clinical and therapeutic landscape, even in combination with stem cell biology
Potential Reparative Role of Resident Adult Renal Stem/Progenitor Cells in Acute Kidney Injury
No full textHuman kidney is particularly susceptible to ischemia and toxins with consequential tubular necrosis and activation of inflammatory processes. This process can lead to the acute renal injury, and even if the kidney has a great capacity for regeneration after tubular damage, in several circumstances, the normal renal repair program may not be sufficient to achieve a successful regeneration. Resident adult renal stem/progenitor cells could participate in this repair process and have the potentiality to enhance the renal regenerative mechanism. This could be achieved both directly, by means of their capacity to differentiate and integrate into the renal tissues, and by means of paracrine factors able to induce or improve the renal repair or regeneration. Recent genetic fate-tracing studies indicated that tubular damage is instead repaired by proliferative duplication of epithelial cells, acquiring a transient progenitor phenotype and by fate-restricted clonal cell progeny emerging from different nephron segments. In this review, we discuss about the properties and the reparative characteristics of high regenerative CD133(+)/CD24(+) cells, with a view to a future application of these cells for the treatment of acute renal injury
MicroRNAs in glomerular diseases from pathophysiology to potential treatment target
No full textMiRNAs are regulators of gene expression in diverse biological and pathological courses in life. Their discovery may be considered one of the most important steps in the story of modern biology. miRNAs are packed within exosomes and released by cells for cellular communications; they are present in bodily fluids. Their study opens the way for understanding the pathogenetic mechanisms of many diseases; furthermore, as potential candidate biomarkers, they can be measured in bodily fluids for non-invasive monitoring of disease outcomes. The present review highlights recent advances in the role of miRNAs in the pathogenesis of primary and secondary glomerulonephritides such as IgA nephropathy, focal segmental glomerular sclerosis, lupus nephritis and diabetic nephropathy. The identification of reciprocal expression of miRNAs and their target genes provides the molecular basis for additional information on the pathogenetic mechanisms of kidney diseases. Finally, recent findings demonstrate that miRNAs can be considered as potential targets for novel drugs. © The Authors Journal compilatio
Clinical Application of Human Urinary Extracellular Vesicles in Kidney and Urologic Diseases
No full textExtracellular vesicles (EVs) have been isolated in different body fluids, including urine. The cargo of urinary EVs is composed of nucleic acids and proteins reflecting the physiological and possibly pathophysiological state of cells lining the nephron and the urinary tract. Urinary EVs have been confirmed to contain low amounts of various types of RNA that play a role in intercellular communication by transferring genetic information. This communication through EV RNAs includes both continuation of normal physiological processes and conditioning in disease mechanisms. Although proteins included in urinary EVs represent only 3% of the whole-urine proteome, urinary EVs can influence cells in the renal epithelia not only by delivering RNA cargo, but also by delivering a wide range of proteins. Since urine is a readily available biofluid, the discovery of EVs has opened a new field of biomarker research. The potential use of urinary EV RNAs and proteins as diagnostic biomarkers for various kidney and urologic diseases is currently being explored. Here, we review recent studies that deal in identifying biomarker candidates for human kidney and urologic diseases using urinary EVs and might help to understand the pathophysiology
New findings showing how DNA methylation influences diseases
No full textIn 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells. Major differences have been found between differentiated cells and stem cells. Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases, such as Parkinson's disease and Huntington's disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are "silenced" by the methylation of CpG sites in some of their regions. Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition, recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence
AQP5: Renal Aquaporins Family Got a New Member
No full textIn an attempt to investigate the regenerative potential of adult multipotent renal progenitor/stem cells (ARPCs) isolated from human kidneys (Sallustio et al., 2009) we characterized them for the expression of aquaporins. ARPCs expressed measurable levels of the proximal tubule-specific AQP1, both at mRNA and protein levels. When ARPCs were differentiated in vitro into epithelial cells, the expression of the collecting duct-specific AQP2 was also induced.
Surprisingly, ARPCs also expressed measurable levels of AQP5, an aquaporin known to be selectively expressed in lung, salivary and lachrymal glands in mammals. This evidence prompted us to investigate the presence and the localization of AQP5 in the mammalian kidney.
Total RNA was isolated from adult human, rat and mouse kidneys and subjected to RT-PCR. Interestingly, AQP5 transcripts were found in all the species tested.
Western blotting analysis, revealed an AQP5 band of 27 kDa as well as a glycosylated form. Consistent with that, neither the transcript nor the protein was found in AQP5 null mice. AQP5 abundance was higher in the renal cortex than in the medulla.
Immunolocalization indicated that AQP5 was expressed at the apical membrane of the cortical collecting ducts (CCDs) epithelial cells with negligible staining in the inner medulla. Triple immunostaining indicated that, in rat CCDs, AQP5 did not colocalize either with AQP2 or with the intercalated cells marker V-ATPase, suggesting a cell specific expression of AQP5 in cells not expressing AQP2 but likely involved in water reabsorption. The ratio between AQP2- and AQP5-expressing cells was approximately 3:1.
In conclusion, the expression of AQP5 in the ARPCs, might suggest a role in the differentiation/regeneration processes of the collecting duct epithelial cells. Moreover, its constitutive expression at the apical membrane in the CCD, renders AQP5 a possible target for improving water reabsorption in the collecting duct when AQP2 apical expression is unpaired as in nephrogenic diabetes insipidus
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