51 research outputs found
Corrigendum to FGF23-regulated production of fetuin-A (AHSG) in osteocytes [Bone 83 (2016) 35-47]
No full textRefers to: D. Mattinzoli, M.P. Rastaldi, M. Ikehata, S. Armelloni, C. Pignatari, L.A. Giardino, M. Li, C.M. Alfieri, A. Regalia, D. Riccardi, P. Messa
FGF23-regulated production of Fetuin-A (AHSG) in osteocytes
Bone, Volume 83, February 2016, Pages 35-4
The sclerosing glomerulus in mice and man: Novel insights
No full textPURPOSE OF REVIEW: Segmental glomerulosclerosis is the end-point of a series of processes with have podocyte damage as a common denominator. This review summarizes the important advances that have been made in the past 2 years leading to the comprehension of several molecular mechanisms of regulation of podocyte physiology and pathology. RECENT FINDINGS: From recent studies it has become clear that the dynamic cytoskeleton of podocyte foot processes has to be highly regulated to maintain cell shape and function. The importance of intracellular calcium in this process has started to be revealed, together with the channels and the organelles appointed to calcium entry and buffering.Novel data highlight the centrality and the complexity of the mammalian target of rapamycin pathways, which are implicated in the regulation of autophagy. Similarities between podocytes and neuronal cells have been extended to the process of dynamin-regulated endocytosis, and further data in mice and humans provide support to the idea that podocytes can be directly targeted by old and new drugs. SUMMARY: Research is bringing numerous advances regarding the role of podocytes in the development of glomerulosclerosis, which can lead to novel and specific therapeutic approaches, as well as to a more rational use of drugs already in use. Consequently, renal biopsy becomes the indispensable instrument not only for diagnosis but also to precisely detect molecular therapeutic targets and guide personalized therapy
Dog as model for down-expression of E-cadherin and beta-catenin in tubular epithelial cells in renal fibrosis.
No full textMechanism of renal fibrosis leading to end stage kidney remains still a challenge of interest in humans. The pathogenesis of chronic kidney disease is characterized by progressive loss of kidney function and fibrosis. The mechanism of epithelial-mesenchymal transition (EMT) has been predominantly studied in in vitro studies, and we previously demonstrated the EMT of tubular epithelial cells in dogs. In this study, we examined and quantified the modifications of cadherin-catenin complex by immunohistochemistry of E-cadherin and beta-catenin and the mesenchymal marker vimentin in 25 dogs with three different spontaneous inflammatory renal diseases. Results showed a significant down-expression of levels of E-cadherin and beta-catenin directly correlated with the tubular-interstitial damage (TID). In TID grades 2 and 3, E-cadherin expression was significantly reduced (p < 0.001). beta-catenin expression was overall similar to E-cadherin. The mesenchymal-associated protein, vimentin, was de novo identified in tubules within areas of inflammation. In this work, we identified the loss of cadherin or catenin expression as a progressive mechanism in tubulo-interstitial fibrosis, which allows dissociation of structural integrity of renal epithelia and loss of epithelial polarity. The dog might result more significant as model for new therapies
L'approccio alla biopsia renale e le nuove possibilita' diagnostiche: cosa cambia nell'era postgenomica = The renal biopsy in the post-genomic era
No full textHistological and immunohistological examination of renal biopsy material is the method of choice for the diagnosis of glomerular and interstitial renal disease. However, our understanding of renal damage is still largely incomplete because of the limited knowledge of the etiology and pathogenesis of numerous kidney diseases. For this reason, we still provide unspecific treatment to kidney patients, which is generally aimed at counteracting inflammatory alterations and slowing progression towards renal failure, without intervening directly in the cause of the disease. The recent development of the ''omics'' (genomics, proteomics, metabolomics) following the enormous progress of high-throughput technologies and information technology tools is profoundly transforming our knowledge in every biomedical field, including nephrology. It is expected that in a very short time a better understanding of both physiological and pathological events in the kidney will translate into different therapeutic strategies, possibly targeted to individual needs. Nephrologists and renal pathologists must take these changes into account and realize that a new approach to renal biopsy is urgently required. Renal biopsy material has in fact an enormous importance in the generation of new knowledge and in the validation of experimental results from high-throughput technologies and animal models. Furthermore, it is conceivable that a new classification of renal diseases will be needed soon as a result of the improved knowledge. For these reasons, renal biopsy material should be adequately processed and preserved according to modern methods, and collaborative projects should be fostered to achieve standardized methods and avoid a waste of energy in singular efforts
Epithelial-mesenchymal transition (EMT) of renal tubular cells in canine glomerulonephritis
No full textTubulo-interstitial fibrosis in dogs may result from primary injury to the interstitium or develop secondary to other renal diseases. As in human renal pathology, tubular epithelial cells (TEC) are believed to actively participate in the mechanisms of renal fibrosis. In this study, we examined the changes in the tubular epithelial component in two specific canine diseases. Immunohistochemistry showed the expression of the epithelial marker cytokeratin, the smooth muscle marker α-SMA, the mesenchymal marker vimentin and PCNA in 20 dogs with membranous glomerulonephritis and membrano-proliferative glomerulonephritis. Results showed that the loss of the epithelial marker in TEC was directly correlated to the grade of tubulo-interstitial disease present and independent of the type of glomerulonephritis. Varying degrees of vimentin positivity were detected in tubular epithelium in areas of inflammation, and low numbers of scattered α-SMA-positive cells were also observed. Immunohistochemistry showed that epithelial tubular cells lose their cytokeratin staining characteristics and transdifferentiate into cells exhibiting key mesenchymal immunophenotypic feature of vimentin-positive staining in both diseases investigated. The integrity of the tubular basement membrane is likely to be fundamental in maintaining the epithelial phenotype of TEC. Animal models provide opportunities for investigating the pathogenesis of renal fibrosis in humans
Espressione di markers neuronali nel testicolo umano azoospermico con Sertoli Cell Only Syndrome
No full textCurrent indications to parathyroidectomy in CKD patients before and after renal transplantation
No full textSecondary hyperparathyroidism (SHP) is one of the most challenging complications in the most advanced stages of end-stage renal disease. In the last decade, newly available medical tools have greatly increased the possibilities for controlling SHP. However, one of these tools, cinacalcet, has not yet been approved for its use in transplanted patients and the evidence for its safety in this clinical setting is still incomplete. For these reasons, many questions still remain open for the clinical nephrologist: when to consider a parathyroidectomy (PTX) in a patient on a waiting list for kidney transplant (KTx); when to recommend PTX after KTx; when could a regression of parathyroid hyperplasia be expected at any time after KTx. In the present paper, we will briefly deal with these questions in the light of an unusual clinical case
FGF23-regulated production of Fetuin-A (AHSG) in osteocytes
No full textIntroduction: AHSG, a serum glycoprotein with recognized anti-calcification activity, has also been suggested to modulate both bone formation and resorption. Though the bulk of AHSG is mostly synthesized in the liver, it has been claimed that also bone cells might produce it. However, the extent of the bone AHSG production and the potential controlling factors remain to be definitively proven.A relevant number of studies support the notion that FGF23, a bone-derived hormone, not only regulates the most important mineral metabolism (MM) related factors (phosphate, parathyroid hormone, vitamin D, etc.), but might be also involved in cardiovascular (CV) outcome, both in chronic kidney disease (CKD) patients and in the general population. Furthermore, in addition to some direct autocrine and paracrine effects in bone, FGF23 has been suggested to interact with AHSG. In this study we investigated if AHSG is really produced by bone cells, and if its bone production is related and/or controlled by FGF23, using cultured bone cells, according to a new method recently published by our group. Results: Our data show that AHSG is consistently produced in osteocytes and to a far lesser extent in osteoblasts. Both FGF23 addition to the culture medium and its over-expression in osteocytes were associated with a consistent increase of both AHSG mRNA and protein, while FGF23 silencing was followed by opposite effects. Though most of these results were largely affected by the blockage of FGF23 receptors, the role of these receptors in the different experimental sets is still not completely clarified. In addition, we found that FGF23 and AHSG proteins co-localized both in cytoplasm and nucleus, which suggests a possible reciprocal interactivity. Conclusions: Our data not only confirm that AHSG is produced in bone, mainly in osteocytes, but show for the first time that its production is modulated by FGF23. Since both proteins play important roles in the bone and cardiovascular pathology, these results add new pieces to the puzzling relationship between bone and vascular pathology, in particular in CKD patients, prompting future investigations in this field
Polymer Nanoparticle Engineering for Podocyte Repair: From in Vitro Models to New Nanotherapeutics in Kidney Diseases
No full textSpecific therapeutic targeting of kidney podocytes, the highly differentiated ramified glomerular cells involved in the onset and/or progression of proteinuric diseases, could become the optimal strategy for preventing chronic kidney disease. With this aim, we developed a library of engineered polymeric nanoparticles (NPs) of tuneable size and surface properties and evaluated their interaction with podocytes. NP cytotoxicity, uptake, and cytoskeletal effects on podocytes were first assessed. On the basis of these data, nanodelivery of dexamethasone loaded into selected biocompatible NPs was successful in repairing damaged podocytes. Finally, a three-dimensional in vitro system of co-culture of endothelial cells and podocytes was exploited as a new tool for mimicking the mechanisms of NP interaction with glomerular cells and the repair of the kidney filtration barrier
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