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10.1242/dmm.020172 http://scihub22266oqcxt.onion/10.1242/dmm.020172 C4610232!4610232!26112172     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26112172&cmd=llinks): Failed to open stream: HTTP request failed! 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Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo |pdf=|usr=}}{{26112172}} gab.com Text Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo JO: Dis Model Mech http://www.kidney.de/pget.php?&tw=1&pmid=26112172 #FOAvip Renal fibrosis is a serious clinical problem resulting in the greatest need for renal replacement therapy. No adequate preventive or curative therapy is available that could be clinically used to target renal fibrosis specifically. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the understanding of the pathogenetic mechanisms involved in renal fibrosis, these models poorly mimic the complex in vivo milieu. Therefore, we here evaluated a precision-cut kidney slice (PCKS) model as a new, multicellular ex vivo model to study the development of fibrosis and its prevention using anti-fibrotic compounds. Precision-cut slices (200-300??m thickness) were prepared from healthy C57BL/6 mouse kidneys using a Krumdieck tissue slicer. To induce changes mimicking the fibrotic process, slices were incubated with TGF?1 (5?ng/ml) for 48?h in the presence or absence of the anti-fibrotic cytokine IFN? (1?µg/ml) or an IFN? conjugate targeted to PDGFR? (PPB-PEG-IFN?). Following culture, tissue viability (ATP-content) and expression of ?-SMA, fibronectin, collagen I and collagen III were determined using real-time PCR and immunohistochemistry. Slices remained viable up to 72?h of incubation, and no significant effects of TGF?1 and IFN? on viability were observed. TGF?1 markedly increased ?-SMA, fibronectin and collagen I mRNA and protein expression levels. IFN? and PPB-PEG-IFN? significantly reduced TGF?1-induced fibronectin, collagen I and collagen III mRNA expression, which was confirmed by immunohistochemistry. The PKCS model is a novel tool to test the pathophysiology of fibrosis and to screen the efficacy of anti-fibrotic drugs ex vivo in a multicellular and pro-fibrotic milieu. A major advantage of the slice model is that it can be used not only for animal but also for (fibrotic) human kidney tissue. Twit Text FOAVip Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo ????Dis Model Mech http://www.kidney.de/pget.php?&tw=1&pmid=26112172 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26112172 #FOAvip English Wikipedia <ref>{{Cite pmid|26112172}}</ref> Precision-cut kidney slices (PCKS) to study development of renal fibrosis and efficacy of drug targeting ex vivo #MMPMID26112172 Poosti F; Pham BT; Oosterhuis D; Poelstra K; van Goor H; Olinga P; Hillebrands JL Dis Model Mech 2015[Oct]; 8 (10): 1227-36 PMID26112172show ga Renal fibrosis is a serious clinical problem resulting in the greatest need for renal replacement therapy. No adequate preventive or curative therapy is available that could be clinically used to target renal fibrosis specifically. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the understanding of the pathogenetic mechanisms involved in renal fibrosis, these models poorly mimic the complex in vivo milieu. Therefore, we here evaluated a precision-cut kidney slice (PCKS) model as a new, multicellular ex vivo model to study the development of fibrosis and its prevention using anti-fibrotic compounds. Precision-cut slices (200-300??m thickness) were prepared from healthy C57BL/6 mouse kidneys using a Krumdieck tissue slicer. To induce changes mimicking the fibrotic process, slices were incubated with TGF?1 (5?ng/ml) for 48?h in the presence or absence of the anti-fibrotic cytokine IFN? (1?µg/ml) or an IFN? conjugate targeted to PDGFR? (PPB-PEG-IFN?). Following culture, tissue viability (ATP-content) and expression of ?-SMA, fibronectin, collagen I and collagen III were determined using real-time PCR and immunohistochemistry. Slices remained viable up to 72?h of incubation, and no significant effects of TGF?1 and IFN? on viability were observed. TGF?1 markedly increased ?-SMA, fibronectin and collagen I mRNA and protein expression levels. IFN? and PPB-PEG-IFN? significantly reduced TGF?1-induced fibronectin, collagen I and collagen III mRNA expression, which was confirmed by immunohistochemistry. The PKCS model is a novel tool to test the pathophysiology of fibrosis and to screen the efficacy of anti-fibrotic drugs ex vivo in a multicellular and pro-fibrotic milieu. A major advantage of the slice model is that it can be used not only for animal but also for (fibrotic) human kidney tissue. äPrecision-cut kidney slices (PCKS) to study development of renal fibro(epmc).pdf DeepDyve Pubget Overpricing