Abstract: PO0602
Histone Deacetylase 6 Inhibition Mitigates Renal Fibrosis by Suppressing TGF-β/SMAD3 and eGFR Signaling Pathways
Session Information
- CKD Mechanisms - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Chen, Xingying, Shanghai East Hospital, Shanghai Tongji University, Shanghai, China
- Zhuang, Shougang, Rhode Island Hospital, Brown University, Providence, United States
Group or Team Name
- Shanghai East Hospital
Background
We have recently shown that histone deacetylase 6 (HDAC6) is critically involved in the pathogenesis of acute kidney injury, however, its role in renal fibrosis remains unclear.
Methods
In this study, we examined the effect of ricolinostat (ACY-1215), a selective inhibitor of HDAC6, on the development of renal fibrosis in a murine model induced by unilateral ureteral obstruction (UUO).
Results
HDAC6 was highly expressed in the kidney following UUO injury, which was coincident with deposition of collagen fibrils and expression of α–smooth muscle actin, fibronectin, and collagen III. Administration of ACY-1215 reduced these fibrotic changes and inhibited UUO-induced expression of transforming growth factor β1 and phosphorylation of Smad3, but increased expression of Smad7. ACY-1215 treatment also suppressed phosphorylation of epidermal growth factor receptor and several signaling molecules associated with renal fibrogenesis, including AKT, signal transducer and activator of transcription 3 and NF-κB in the injured kidney. Furthermore, ACY-1215 was effective in inhibiting dedifferentiation of renal fibroblasts to myofibroblasts in cultured renal interstitial fibroblasts.
Conclusion
Collectively, these results indicate that HDAC6 inhibition can attenuate renal fibrosis development by suppression of TGFβ1 and EGFR signaling.
Funding
- NIDDK Support