Abstract: TH-PO462
Inhibition of Nα-Acetyltransferase Attenuates Renal Interstitial Fibrosis via Modulation of Epithelial-to-Mesenchymal Transition and Inflammation
Session Information
- CKD: Mechanisms - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Son, Jongho, The Catholic Universiry of Korea Yeouido St. Mary's Hospital, Seoul, Korea (the Republic of)
- Chung, Sungjin, The Catholic University of Korea College of Medicine, Seoul, Korea (the Republic of)
- Shin, Seok Joon, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Incheon, Korea (the Republic of)
- Park, Cheol Whee, The Catholic University of Korea College of Medicine, Seoul, Korea (the Republic of)
- Yang, Chul Woo, The Catholic University of Korea College of Medicine, Seoul, Korea (the Republic of)
- Koh, Eun Sil, The Catholic University of Korea College of Medicine, Seoul, Korea (the Republic of)
Background
Nα-acetyltransferase 10 (Naa10), the catalytic subunit of N-acetyltransferase A, has been reported to be involved in the regulation of telomerase activity, DNA damage response, cytokinesis, microtubule reorganization and histone acetylation. This study was designed to investigate whether the pharmacological inhibition of Naa10 could affect the progression of renal tubulointerstitial fibrosis.
Methods
Remodelin 1mg/kg, a Naa10 inhibitor, was administered to the mice for 3 or 7 days following unilateral ureteral obstruction (UUO).
Results
Renal Naa10 expression after UUO was significantly enhanced but reduced by the Naa10 inhibitor remodelin. Masson trichrome and Sirius red staining demonstrated that Naa10 inhibition led to a decrease in renal interstitial fibrosis induced by UUO. In addition, the α-SMA- or TUNEL-positive cells were apparently decreased in obstructed kidneys with administration of remodelin. Furthermore, remodelin inhibited the increase in the mRNA levels of α-SMA, fibronectin, MMP-2, IL-1β, IL-6, TNF-α, TGF-β1 and ColIV without significant changes in mRNA levels of vimentin, E-cadherin and VE-cadherin and protein expressions of Nox1, Nox2, Nox4, SOD1, HO-1, NQO1 and catalase in obstructed kidneys. All these findings were apparent at day 7 after UUO. Collectively, these results indicate that longer treatment of remodelin mitigates UUO-induced renal interstitial fibrosis by affecting epithelial-to-mesenchymal transition (EMT) and inflammation.
Conclusion
Current study suggests that Naa10 inhibition could attenuate renal fibrosis through regulation of certain EMT- and inflammation-related factors.
Funding
- Government Support - Non-U.S.