Next Article in Journal / Special Issue
Tumor Budding: The Name is EMT. Partial EMT.
Previous Article in Journal
Treatment of Established Status Epilepticus
Previous Article in Special Issue
Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases
Article Menu

Export Article

Open AccessArticle
J. Clin. Med. 2016, 5(5), 50;

Tacrolimus Modulates TGF-β Signaling to Induce Epithelial-Mesenchymal Transition in Human Renal Proximal Tubule Epithelial Cells

Centre for Cell Signaling and Inflammation, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK
Renal Disease Research Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin 4, Ireland
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Jane Grant-Kels
Received: 21 November 2015 / Revised: 16 April 2016 / Accepted: 19 April 2016 / Published: 26 April 2016
(This article belongs to the Special Issue Epithelial-Mesenchymal Transition)
Full-Text   |   PDF [3796 KB, uploaded 26 April 2016]   |  


Epithelial-mesenchymal transition (EMT), a process which describes the trans-differentiation of epithelial cells into motile mesenchymal cells, is pivotal in stem cell behavior, development and wound healing, as well as contributing to disease processes including fibrosis and cancer progression. Maintenance immunosuppression with calcineurin inhibitors (CNIs) has become routine management for renal transplant patient, but unfortunately the nephrotoxicity of these drugs has been well documented. HK-2 cells were exposed to Tacrolimus (FK506) and EMT markers were assessed by RT PCR and western blot. FK506 effects on TGF-β mRNA were assessed by RT PCR and TGF-β secretion was measured by ELISA. The impact of increased TGF-β secretion on Smad signaling pathways was investigated. The impact of inhibition of TGF-β signaling on EMT processes was assessed by scratch-wound assay. The results presented in this study suggest that FK506 initiates EMT processes in the HK-2 cell line, with altered expression of epithelial and myofibroblast markers evident. Additionally, the study demonstrates that FK506 activation of the TGF-β/ SMAD pathways is an essential step in the EMT process. Overall the results demonstrate that EMT is heavily involved in renal fibrosis associated with CNI nephrotoxicity. View Full-Text
Keywords: Epithelial-mesenchymal transition; tacrolimus; fibrosis Epithelial-mesenchymal transition; tacrolimus; fibrosis

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top