Abstract: FR-PO185
Functional Role of a Novel Renal Protective Protein TMEM52B in Kidney Fibrosis
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Xue, Rui, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China
- Wan, Qijun, Shenzhen Second People's Hospital, Shenzhen, Guangdong, China
Background
Renal fibrosis, especially tubulointerstitial fibrosis, is the primary pathological hallmark of renal injury and signifies the progression of end-stage renal disease. Through exome sequencing of various human organs and tissues, our study has identified significant enrichment of transmembrane protein 52B (TMEM52B) expression in the kidney, highlighting its close correlation with renal function. Consequently, our upcoming studies aim to elucidate more deeply the exact role and underlying mechanisms of TMEM52B in renal tubular injury, specifically in tubulointerstitial fibrosis.
Methods
We employed CRISPR-Cas9 technology to construct TMEM52B gene system knockout C57BL/6 mice. Subsequently, we performed unilateral ureteral obstruction (UUO) surgery to induce renal injury and tubulointerstitial fibrosis. Following the surgery, we then conducted a series of analyses and proteomics testing to investigate the changes after TMEM52B knockout. Finally, we conducted additional in vitro experiments to further validate the molecular mechanism of TMEM52B in renal fibrosis.
Results
TMEM52B expression was decreased significantly in UUO mice and nearly absent in the kidneys of TMEM52B knockout mice. Tubular injury and fibrosis markers in UUO mice were aggravated by TMEM52B knockout which was preserved with more tubular injury and fibrosis compared to control mice. Proteomic analysis showed Myeloid-Derived Growth Factor (MYDGF) expression was significantly decreased in the kidney tissue of UUO model mice, and further markedly decreased in TMEM52B system knockout UUO model mice. In vitro, TMEM52B expression significantly decreased under TGF-β1 stimulation, and altering TMEM52B levels correspondingly changed MYDGF expression.
Conclusion
Knock-out of TMEM52B could exacerbate tubular injury and alleviate tubulointerstitial fibrosis in UUO mouse model. This process is a cascade coordinated by the regulation of MYDGF. Our findings suggest a critical role of TMEM52B in the pathogenesis of tubular injury and further provide a potential novel therapeutic target for renal fibrosis.