Simple jQuery Dropdowns
Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/31145
Title: Secreted Products of Macrophages Exposed to Calcium Oxalate Crystals Induce Epithelial Mesenchymal Transition of Renal Tubular Cells via RhoA-Dependent TGF-β1 Pathway
Authors: Rattiyaporn Kanlaya
Kitisak Sintiprungrat
Visith Thongboonkerd
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Dec-2013
Citation: Cell Biochemistry and Biophysics. Vol.67, No.3 (2013), 1207-1215
Abstract: Kidney stone disease is associated with renal fibrosis by the unclear mechanisms. We hypothesized that calcium oxalate (CaOx), a major crystalline component of kidney stones, could induce secretion of fibrotic factors from macrophages leading to "epithelial mesenchymal transition/transdifferentiation" (EMT) of renal tubular cells. Western blot analysis revealed an increased level of vimentin (mesenchymal marker) but decreased levels of E-cadherin and cytokeratin (epithelial markers) in MDCK cells treated with "secreted products from CaOx-exposed macrophages" (CaOx-M-Sup). Immunofluorescence study confirmed the increased level of vimentin and decreased level of cytokeratin, and also revealed the increased level of fibronectin (another mesenchymal marker). The data also showed decreased levels and disorganization of F-actin (cytoskeletal marker) and zonula occludens-1 (ZO-1) (tight junction marker) induced by CaOx-M-Sup. ELISA demonstrated the increased level of transforming growth factor-β1 (TGF-β1), the well-defined EMT inducer, in CaOx-M-Sup. Downstream signaling of TGF-β1 was involved as demonstrated by the decreased level of RhoA. Interestingly, pretreatment with a proteasome inhibitor (MG132) could restore RhoA to its basal level, most likely through ubiquitin-proteasome pathway (UPP). Moreover, MG132 successfully sustained cytoskeletal assembly and tight junction, and could prevent the cells from EMT. Altogether, these data demonstrate for the first time that CaOx-M-Sup could induce EMT in renal tubular cells by TGF-β1 signaling cascade via RhoA and UPP. This may be, at least in part, the underlying mechanism for renal fibrosis in kidney stone disease. © 2013 Springer Science+Business Media New York.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84888314137&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/31145
ISSN: 10859195
Appears in Collections:Scopus 2011-2015

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.