Original ContributionThe NRF2–heme oxygenase-1 system modulates cyclosporin A-induced epithelial–mesenchymal transition and renal fibrosis
Section snippets
Materials
CsA, cobalt protoporphyrin (CoPP), and SFN were purchased from Sigma (Saint Louis, MO, USA). Antibodies recognizing NRF2, lamin B, and β-tubulin were obtained from Santa Cruz Biotechnology (Santa Cruz, CA, USA). E-cadherin antibody was purchased from BD Biosciences (Mississauga, ON, Canada) and α-SMA antibody was obtained from DAKO (Glostrup, Denmark). The reporter plasmid containing the human NQO1 ARE was a gift from Dr. Nobunao Wakabayashi (Johns Hopkins University, Baltimore, MD, USA).
CsA induces EMT marker changes in normal rat renal tubular epithelial cells
It has been demonstrated that CsA treatment results in morphologic changes, including cell elongation and junctional disruption, with an increased expression of the myofibroblast-specific marker α-SMA in human proximal tubular cells [15], [29]. This supports the possibility that EMT plays a role in CsA-induced tubulointerstitial fibrosis. Therefore, we have examined the effects of CsA on EMT marker changes in rat renal tubular epithelial NRK cells. As an EMT marker, the expression of the
Discussion
Tissue fibrosis can result from inappropriate repair processes after tissue damage, which can be caused by various stimuli, including infection, inflammation, and chemical stress [14]. Fibrosis accompanies the excessive deposition of ECM, leading to the destruction of tissues and eventual organ failure. Myofibroblasts play a central role in the process of fibrosis by producing ECM. EMT has been implicated as the primary mechanism of renal fibrogenesis through the generation of mesenchymal-type
Acknowledgments
We thank Patrick M. Dolan (Johns Hopkins University, Baltimore, MD, USA) for maintaining and genotyping the mice. This work was supported by a National Research Foundation of Korea grant, funded by the Korean government (2009-0066689), to M.-K. Kwak and by NIH Grant CA94076 to T.W. Kensler.
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These authors contributed equally to this work.