eng URI http://hdl.handle.net/10795/2970 βιολογία Renal fibrosis is the common anatomical feature underlying the progression of chronic kidney disease, a leading cause of morbidity and mortality worldwide. In a previous study, we demonstrated that during development of renal fibrosis in a rat model of unilateral ureteric obstruction, calreticulin (CRT) is up-regulated in tubular epithelial cells (TECs). In the present study, we used in vitro and in vivo approaches to examine the role of CRT in TECs and its contribution to the progression of fibrosis. In cultured renal TECs, CRT overexpression induced acquisition of an altered, profibrotic cellular phenotype. Consistently, the opposite effects were observed for CRT knockdown. Subsequently, we confirmed that critical changes observed in vitro were also apparent in tubular cells in vivo in the animal model of unilateral ureteric obstruction. In agreement with these results, we demonstrate that substantial (50%) reduction in the expression of CRT reduced the development of tubulointerstitial fibrosis at a comparable level through regulation of inflammation, transcriptional activation, transforming growth factor b1eassociated effects, and apoptosis. In summary, our findings establish that CRT is critically involved in the molecular mechanisms that drive renal fibrosis progression and indicate that inhibition of CRT expression might be a therapeutic target for reduction of fibrosis and chronic kidney disease development. 15 pp. LOMv1.0 creator LOMv1.0 publisher LOMv1.0 Scientific Coordinator LOMv1.0 Project Executing Organisation 2013-11 Digital Library of the Operational Programme "Education and Lifelong Learning" abstract types Text Renal fibrosis Calreticulin (CRT) Profibrotic cellular Molecular mechanisms Epithelial cells http://www.sciencedirect.com/science/article/pii/S000294401300535X 3190630 application/pdf http://repository.edulll.gr/edulll/bitstream/10795/2970/2/2970_1.7_%ce%94%ce%97%ce%9c_11_9_13.pdf URI http://hdl.handle.net/10795/2970 LOMv1.0creator 2016-04-27T10:44:31Z LOMv1.0validator 2016-04-27T10:44:31Z LOMv1.0 gre no no Copyright EYD-EPEDBM (Operational Programme "Education and Lifelong Learning")