Date: Monday, June 3, 2019
Session Name: Poster Session C: Immunosuppression Preclinical Studies
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Our study was to detect the effects of Bortezomib and Smurf1 in the EMT and allograft renal interstitial fibrosis.
*Methods: Biomarkers of EMT, as well as Smurf1, were examined in human proximal tubular epithelial cells (HK-2) treated with tumor necrosis factor-alpha (TNF-α) in various doses or at various time points by Western Blotting or qRT-PCR. We also knocked-down or overexpressed Smurf1 in HK-2 cells then detected the changes of biomarkers of EMT induced by TNF-α. Furthermore, rat allograft renal transplantation model was established and intervened by Bortezomib. Allograft renal tissues from rats were also collected and prepared for HE, Masson’s trichrome, immunohistochemical staining and western blotting assays.
*Results: As a result, we found that TNF-α significantly promoted the development of EMT in a time-dependent and dose-dependent manner through Smurf1/Akt/mTOR/P70S6K signaling pathway in vivo and in vitro. More importantly, Bortezomib could alleviate the progression of EMT and allograft renal interstitial fibrosis in vivo and in vitro by inhibiting the effects of TNF-α and expression of Smurf1.
*Conclusions: Smurf1 maybe play a critical role in the development of EMT induced by TNF-α in HK-2 CELLS and allograft transplanted kidneys. Bortezomib can attenuate the Sumrf1-mediated progression of EMT and allograft renal interstitial fibrosis, which could be suggested as a novel choice for the prevention and treatment of allograft renal interstitial fibrosis.
To cite this abstract in AMA style:Tan R, Wang Z, Fei S, Han Z, Tao J, Ju X, Gu M. Bortezomib Attenuates the Progression of Epithelial to Mesenchymal Transition through Smurf1 Akt mTOR P70S6K Pathway in Rat Allograft Renal Interstitial Fibrosis Model [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/bortezomib-attenuates-the-progression-of-epithelial-to-mesenchymal-transition-through-smurf1-akt-mtor-p70s6k-pathway-in-rat-allograft-renal-interstitial-fibrosis-model/. Accessed April 20, 2021.
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