Abstract: TH-PO1091
ACSM3 Protects Kidney Aging and Fibrosis by Cellular Senescence via Histone Acetylation
Session Information
- CKD: Mechanisms - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Wu, Yiting, Sichuan University, Chengdu, Sichuan, China
- Ma, Liang, Sichuan University, Chengdu, Sichuan, China
- Fu, Ping, Sichuan University, Chengdu, Sichuan, China
Background
Cellular senescence is associated with renal disease progression. Accelerated tubular cell senescence promotes the pathogenesis of renal fibrosis caused by natural aging and disease.
Methods
Proteomic analysis and IHC staining were made to show Acsm3 expression. Acsm3 KO and overexpressed(AAV) mice were performed UUO surgeries. Renal fibrosis was measured by qPCR and Western Blot. SA-β-gal staining and γH2AX IHC staining was used to check senescence. IF staining was to locate Acsm3.
Results
Cellular senescence happened in both elderly mice and UUO mice. Acsm3 is the No.1 increased protein in elderly mice via proteomic sequencing. ACSM3 was positively correlated with age and eGFR. The KO of Acsm3 could induce renal fibrosis with increased α-SMA etc. Senescence was increased with growth SA-β-gal and γH2AX. Overexpressing Acsm3 by AAV, the fibrosis and senescence became less. H3K27AC was the most significant histone modification among others. Locating ACSM3 in cell mitochondria, there was an ACSM3 nuclear translocation treated with TGF-β. Overexpression of ACSM3 can reduce acetyl-CoA in the nucleus.
Conclusion
Acsm3 may be a protector for renal fibrosis by inhibiting cellular senescence of tubular epithelial cells. The underlying mechanism may be the histone acetylation modification.