Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells
Abstract
:1. Introduction
2. Experimental Section
3. Results and Discussion
3.1. FK506 Treatment Resulted in Significant Increases in Both LDH Release and Resazurin Conversion Without Affecting RPTEC Proliferation
3.2. FK506 Treatment Induced Morphological Alterations in the RPTECs
3.3. FK506 Induced Myofibroblast Transition in the RPTEC Cells
3.4. FK506 Increased TGF-β1 mRNA Levels and TGF-β1 Peptide Release from RPTEC Cells, with Concomitant Increases in Phospho-Smad2 Whole Cell Protein Levels
3.5. Treatment of RPTEC cells with FK506 Induced Increased Cell Migration Which Was Alleviated Following Co-Treatment with a TGF-β RI Kinase Inhibitor
3.6. Pre-Incubation with a TGF-β Receptor 1 Kinase Inhibitor Completely Blocks Smad 2 Activation and Prevents Induction of EMT Markers by FK506
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
α-SMA | Alpha smooth muscle actin |
ANOVA | One way Analysis of Variance |
BrdU | Bromodeoxyuridine |
CaCl2 | Calcium Chloride |
CaN | Calcineurin Phosphatase |
cDNA | Complimentary deoxyribonucleic acid |
CNI(s) | Calcineurin inhibitor(s) |
CKD | Chronic Kidney Disease |
CO2 | Carbon Dioxide |
CpN | Cyclophilin |
CsA | Cyclosporine A |
Ctrl | Control |
DMEM | Dulbecco’s modified Eagle’s medium |
DMEM/F-12 | DMEM/Nutrient mix F-12 |
DMSO | Dimethylsulfoxide |
DNA | Deoxyribonucleic acid |
ECM | Extracellular matrix |
ELISA | Enzyme linked immunosorbent assay |
EMT | Epithelial-Mesenchymal Transition |
ESRD | End Stage Renal Disease |
FK506 | FK506, Tacrolimus |
FKBP12 | FK506 Binding Protein 12 |
HK-2 | Human Kidney-2 |
kDA | Kilodaltons |
LDH | Lactate Dehydrogenase |
Mg | Milligrams |
mM | Millimolar |
MMP | Matrix metalloproteinase |
NaCl | Sodium Chloride |
NFAT | Nuclear Factor of Activated T-cells |
NFATC | Cytosolic Nuclear Factor of Activated T-Cells |
NFATN | Nuclear Nuclear Factor of Activated T-Cells |
Ng | Nanograms |
nM | Nanomolar |
PCR | Polymerase chain reaction |
Pg | Picograms |
PTECs | Proximal Tubular Epithelial Cells |
RNA | Ribonucleic acid |
rRNA | Ribosomal ribonucleic acid |
RT-PCR | Real Time-polymerase chain reaction |
SDS | Sodium dodecyl sulphate |
SDS-PAGE | SDS-polyacrylamide gel electrophoresis |
S.E.M | Standard error of the mean |
TGF-β1 | Transforming growth factor beta 1 |
TIF | Tubulointerstitial fibrosis |
U | Units |
µg | Micrograms |
µL | Microlitres |
μM | Micromolar |
v/v | Volume per Volume |
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Bennett, J.; Cassidy, H.; Slattery, C.; Ryan, M.P.; McMorrow, T. Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells. J. Clin. Med. 2016, 5, 50. https://doi.org/10.3390/jcm5050050
Bennett J, Cassidy H, Slattery C, Ryan MP, McMorrow T. Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells. Journal of Clinical Medicine. 2016; 5(5):50. https://doi.org/10.3390/jcm5050050
Chicago/Turabian StyleBennett, Jason, Hilary Cassidy, Craig Slattery, Michael P. Ryan, and Tara McMorrow. 2016. "Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells" Journal of Clinical Medicine 5, no. 5: 50. https://doi.org/10.3390/jcm5050050