Abstract: SA-PO0419
Decoding the Antiperitoneal Fibrosis Axis: SND1-Guided CDC14B mRNA Splicing Inhibits Peritoneal Mesothelial Cell Senescence
Session Information
- Home Dialysis: Science and Cases, from Lab to Living Room
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 802 Dialysis: Home Dialysis and Peritoneal Dialysis
Authors
- Li, Shuting, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Ji, Yue, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Zhu, Silin, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Luo, Dan, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Mo, Min, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Liu, Mi, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Luo, Qimei, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
- Dou, Xianrui, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China
Background
Alternative splicing serves as a pivotal RNA processing mechanism that amplifies transcriptomic complexity and proteomic diversity in fibrotic disorders. Emerging evidence underscores the functional significance of RNA-binding protein-regulated splicing variants during fibrogenesis. Staphylococcal nuclease and tudor domain containing 1 gene (SND1) is an RNA-binding protein implicated in extracellular matrix remodeling; however, its regulatory role in peritoneal dialysis (PD)-associated peritoneal fibrosis and the associated splicing circuitry remains mechanistically undefined.
Methods
Through analysis of single-cell RNA sequencing data derived from PD patients, we identified SND1 as a hub regulator in fibrogenic niches. Subsequent bulk RNA sequencing with rMATS-mediated alternative splicing profiling deciphered SND1-mediated splicing landscape rewiring. The effects of SND1 on peritoneal mesothelial cell(PMC) senescence and peritoneal fibrosis were detected through a mouse PD model with AAV overexpression or knockdown of SND1 in vivo and in vitro primary PMCs models.
Results
SND1 expression was downregulated in PMCs of peritoneal fibrosis models. Bulk RNA-seq showed that knockdown of SND1 in PMCs predominantly dysregulated pathways related to cellular senescence, cell cycle progression, extracellular matrix synthesis, and inflammatory responses. rMATS analysis of bulk RNA-seq data from SND1-knockdown and control cells identified 153 differential alternative splicing events, with exon skipping being the most prevalent type. Notably, cell division cycle 14B(CDC14B) was identified as a key downstream target of SND1. Reduced SND1 expression induced truncation of exon 2 in CDC14B transcripts, leading to diminished full-length CDC14B protein production, cell cycle arrest in PMCs , and subsequent senescence and peritoneal fibrosis progression. In animal studies, AAV-mediated SND1 overexpression attenuated peritoneal fibrosis, whereas SND1 knockdown exacerbated fibrotic severity.
Conclusion
SND1 in PMCs suppresses cellular senescence and fibrogenesis by regulating CDC14B alternative splicing. This study reveals a novel mechanism underlying PD-associated peritoneal fibrosis and highlights SND1 as a potential therapeutic target for preventing or mitigating peritoneal fibrosis.
Funding
- Government Support – Non-U.S.