scholarly journals Epithelial to Mesenchymal Transition in Madin-Darby Canine Kidney Cells Is Accompanied by Down-regulation of Smad3 Expression, Leading to Resistance to Transforming Growth Factor-β-induced Growth Arrest

2002 ◽  
Vol 278 (5) ◽  
pp. 3251-3256 ◽  
Author(s):  
Francisco J. Nicolás ◽  
Kerstin Lehmann ◽  
Patricia H. Warne ◽  
Caroline S. Hill ◽  
Julian Downward
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Growth Arrest ◽  
Transforming Growth Factor Β ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Mesenchymal Transition ◽  
Smad3 Expression ◽  
Darby Canine Kidney ◽  
Canine Kidney

Ectodomain shedding of pro-TGF-α is required for COX-2 induction and cell survival in renal medullary cells exposed to osmotic stress

2007 ◽  
Vol 293 (6) ◽  
pp. C1971-C1982 ◽  
Author(s):  
Christoph Küper ◽  
Helmut Bartels ◽  
Maria-Luisa Fraek ◽  
Franz X. Beck ◽  
Wolfgang Neuhofer
Keyword(s):  
Osmotic Stress ◽  
Cell Survival ◽  
Transforming Growth Factor ◽  
Ectodomain Shedding ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Cox 2 ◽  
Darby Canine Kidney ◽  
Canine Kidney ◽  
Medullary Cells

In the renal medulla, cyclooxygenase (COX)-2 is induced by osmotic stress as present in this kidney region during antidiuresis. Increasing evidence suggests that EGF receptor (EGFR) signaling is involved in this process. The aim of the present study was to examine the mechanisms responsible for COX-2 expression and PGE2 production during hypertonic conditions and to identify potential autocrine/paracrine EGFR ligands. Immunohistochemisty and Western blot analysis revealed abundant expression of the pro-EGFR ligand pro-transforming growth factor (TGF)-α in renal medullary cells in vivo and in cultured Madin-Darby canine kidney cells. In Madin-Darby canine kidney cells, hypertonicity rapidly increased TNF-α converting enzyme (TACE)-dependent ectodomain shedding of pro-TGF-α; phosphorylation of EGFR, p38, and ERK1/2; expression of COX-2; and production of PGE2. Conversely, TACE inhibition prevented TGF-α release; EGFR, p38, and ERK1/2 activation; and COX-2 expression. Furthermore, cell survival was reduced substantially, a response that could be reversed by the addition of PGE2. Simultaneous addition of recombinant TGF-α during TACE inhibition restored EGFR and MAPK phosphorylation, COX-2 expression, PGE2 production, and cell survival during osmotic stress. These results indicate that hypertonicity induces TACE-mediated ectodomain shedding of pro-TGF-α, which subsequently activates COX-2 expression in an autocrine/paracrine fashion, via EGFR and MAPKs. We conclude that tonicity-induced TGF-α release is required for COX-2 expression, PGE2 synthesis, and survival of renal medullary cells during osmotic stress.

scholarly journals Calreticulin Represses E-cadherin Gene Expression in Madin-Darby Canine Kidney Cells via Slug

2006 ◽  
Vol 281 (43) ◽  
pp. 32469-32484 ◽  
Author(s):  
Yasushi Hayashida ◽  
Yoshishige Urata ◽  
Eiji Muroi ◽  
Takaaki Kono ◽  
Yasuyoshi Miyata ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Gene Transfection ◽  
Cell Phenotype ◽  
Boyden Chamber ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Mesenchymal Transition ◽  
Darby Canine Kidney ◽  
Canine Kidney ◽  
E Cadherin

Calreticulin (CRT) is a multifunctional Ca2+-binding molecular chaperone in the endoplasmic reticulum. In mammals, the expression level of CRT differs markedly in a variety of organs and tissues, suggesting that CRT plays a specific role in each cell type. In the present study, we focused on CRT functions in the kidney, where overall expression of CRT is quite low, and established CRT-overexpressing kidney epithelial cell-derived Madin-Darby canine kidney cells by gene transfection. We demonstrated that, in CRT-overexpressing cells, the morphology was apparently changed, and the original polarized epithelial cell phenotype was destroyed. Furthermore, CRT-overexpressing cells showed enhanced migration through Matrigel®-coated Boyden chamber wells, compared with controls. E-cadherin expression was significantly suppressed at the protein and transcriptional levels in CRT-overexpressing cells compared with controls. On the other hand, the expression of mesenchymal protein markers, such as N-cadherin and fibronectin, was up-regulated. We also found that the expression of Slug, a repressor of the E-cadherin promoter, was up-regulated by overexpression of CRT through altered Ca2+ homeostasis, and this led to enhanced binding of Slug to the E-box element in the E-cadherin promoter. Thus, we conclude that CRT regulates the epithelial-mesenchymal transition-like change of cellular phenotype by modulating the Slug/E-cadherin pathway through altered Ca2+ homeostasis in cells, suggesting a novel function of CRT in cell-cell interaction of epithelial cells.

scholarly journals Inhibition by brefeldin A of protein secretion from the apical cell surface of Madin-Darby canine kidney cells.

1991 ◽  
Vol 266 (27) ◽  
pp. 17729-17732 ◽  
Author(s):  
S.H. Low ◽  
S.H. Wong ◽  
B.L. Tang ◽  
P. Tan ◽  
V.N. Subramaniam ◽  
...  
Keyword(s):  
Cell Surface ◽  
Protein Secretion ◽  
Apical Cell ◽  
Brefeldin A ◽  
Kidney Cells ◽  
Madin Darby Canine Kidney ◽  
Darby Canine Kidney ◽  
Canine Kidney

scholarly journals Noncoding RNAs as Promising Diagnostic Biomarkers and Therapeutic Targets in Intestinal Fibrosis of Crohn’s Disease: The Path From Bench to Bedside

2020 ◽  
Author(s):  
Long-Yuan Zhou ◽  
Si-Nan Lin ◽  
Florian Rieder ◽  
Min-Hu Chen ◽  
Sheng-Hong Zhang ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Noncoding Rnas ◽  
Transforming Growth Factor Β ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Fibrotic Diseases ◽  
Endothelial To Mesenchymal Transition

Abstract Fibrosis is a major pathway to organ injury and failure, accounting for more than one-third of deaths worldwide. Intestinal fibrosis causes irreversible and serious clinical complications, such as strictures and obstruction, secondary to a complex pathogenesis. Under the stimulation of profibrotic soluble factors, excessive activation of mesenchymal cells causes extracellular matrix deposition via canonical transforming growth factor-β/Smads signaling or other pathways (eg, epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition) in intestinal fibrogenesis. In recent studies, the importance of noncoding RNAs (ncRNAs) stands out in fibrotic diseases in that ncRNAs exhibit a remarkable variety of biological functions in modulating the aforementioned fibrogenic responses. In this review, we summarize the role of ncRNAs, including the emerging long ncRNAs and circular RNAs, in intestinal fibrogenesis. Notably, the translational potential of ncRNAs as diagnostic biomarkers and therapeutic targets in the management of intestinal fibrosis is discussed based on clinical trials from fibrotic diseases in other organs. The main points of this review include the following: • Characteristics of ncRNAs and mechanisms of intestinal fibrogenesis • Wide participation of ncRNAs (especially the emerging long ncRNAs and circular RNAs) in intestinal fibrosis, including transforming growth factor-β signaling, epithelial-to-mesenchymal transition/endothelial-to-mesenchymal transition, and extracellular matrix remodeling • Translational potential of ncRNAs in the diagnosis and treatment of intestinal fibrosis based on clinical trials from fibrotic diseases in other organs

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