Session Time: 7:30pm-8:30pm
Presentation Time: 7:30pm-7:40pm
*Purpose: Chronic renal graft dysfunction is characterized by inflammation, tubular injury, and interstitial fibrosis. We have confirmed that endothelial-mesenchymal transition (EndMT) was one of important sources to allograft interstitial fibrosis. However, whether and how autophagy contributes to renal allograft fibrosis remains unclear. ATG16L is a critical autophagy-related gene (ARG) for autophagosome formation.
*Methods: The GEO database was searched and data was retreived. 60 allograft tissues were collected from renal transplant recipients with chronic allograft dysfunction (CAD) to explore the autophagy in kidney transplantation. Moreover, cell culture was performed and human umbilical artery endothelial cells (HUAECs) and human renal glomerular endothelial cells (HRGECs) were induced by TNF‐α. Autophagy in endothelial cells was examined and signaling pathway was tested.
*Results: Here, we observed ATG16L, as one significant differential ARG, was lower expression in chronic allograft dysfunction (CAD) group compared with non-rejecting by analyzing data sets from Gene Expression Omnibus (GEO). The same results were obtained in 60 kidney transplanted patients with CAD that there are less autophagosome and autolysosome in transplated kidneys, and downregulation of autophagy related to poor prognosis. In addition, we found that TNF‐α could induce EndMT in human umbilical artery endothelial cells (HUAECs) and human renal glomerular endothelial cells (HRGECs), and knockdown of ATG16L facilitated this process. In vivo, we demonstrated abundance of ATG16L related to the dynamic autophagic flux change along different stages of kidney transplantation and autophagy activation alleviated the progression of EndMT, interstitial extracellular matrix deposition and inflammatory cell infiltration by increasing ATG16L expression. Mechanistically, loss of ATG16L specifically in endothelial cells reduced SQSTM1/p62-dependent autophagic degradation of NF-κB and resulted in production of TNF‐α.
*Conclusions: ATG16L-dependent autophagy served as a negative regulator of TNF‐α-induced inflammation, EndMT and the development of renal graft fibrosis, therefore, autophagy could be used as a potential therapeutic target for chronic renal graft rejection.
To cite this abstract in AMA style:Gui Z, Wang Z, Han Z, Tao J, Ju X, Tan R, Gu M. Atg16l-Dependent Autophagy Attenuates Procession of Renal Interstitial Fibrosis in Chronic Renal Graft Dysfunction via Regulating Tumor Necrosis Factor Alpha (tnf-α) Induced Endmt [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/atg16l-dependent-autophagy-attenuates-procession-of-renal-interstitial-fibrosis-in-chronic-renal-graft-dysfunction-via-regulating-tumor-necrosis-factor-alpha-tnf-%ce%b1-induced-endmt/. Accessed June 13, 2021.
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