Abstract: TH-PO1181
Aggravation of Renal Fibrosis by Renal Tubular Epithelial Cell Deficiency of Sesn2 in a Unilateral Ureteral Obstruction Mouse Model
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Sreerama Pramod, Gowda, University of South Florida, Tampa, Florida, United States
- Hall, Nathan, University of South Florida, Tampa, Florida, United States
- Wei, Jin, University of Mississippi School of Medicine, Jackson, Mississippi, United States
- Zheleznova, Nadezhda N., University of South Florida, Tampa, Florida, United States
- Hernandez Soto, Nohely, University of South Florida, Tampa, Florida, United States
- Liu, Ruisheng, University of South Florida, Tampa, Florida, United States
Background
Sestrin2 (Sesn2) is a highly evolutionary conserved protein and involved in different cellular responses to various stresses. Our previous research has demonstrated that Acute kidney injury (AKI) leads to cardiac injury, the anti-diabetic drug metformin preserved cardiac function by upregulating Sesn2 in the heart after AKI. However, the potential function of Sesn2 in kidneys upon AKI or chronic kidney disease (CKD) is unknown. In this study, using a unilateral ureteral obstruction (UUO) mouse model, we obstructed the ureter and induced severe renal fibrosis leading to CKD, and sought to determine if downregulating Sesn2 specifically in the proximal tubular epithelial cells (PTEC), improved or worsened the fibrosis condition in kidneys.
Methods
To seek the relationship between Sesn2 expression and the renal interstitial fibrosis genes, we used human datasets of renal transcriptomic data available on the mRNA microarray dataset GSE66494 and compared healthy and CKD kidney biopsies. We used UUO mouse model to develop renal fibrosis in the kidneys leading to CKD. To specifically understand the role of Sesn2 in PTECs during the development of fibrosis, we used Pax8-Cre/Sesn2fl/fl mice.
Results
In the present study, we initially observed a decrease in Sesn2 expression with increased renal fibrosis in the ureter obstructed kidney as compared to unobstructed kidney in the UUO mouse model. Also, the expression analysis of a panel of mRNAs from the kidney biopsy specimens of CKD patients with healthy control, revealed a negative correlation between Sesn2 and renal fibrosis gene expression. Loss of Sesn2 in renal tubular cells in a UUO-mouse model correlated with a further increase in interstitial fibrosis, macrophage infiltration, myofibroblast proliferation, inflammation and upregulation of kidney injury markers KIM-1 and NGAL.
Conclusion
Our study suggests that loss of Sesn2 in renal tubular epithelial cells further augments the UUO-induced renal interstitial fibrosis. Further investigation into how Sesn2 is downregulated in UUO mouse obstructed kidney and methods to enhance Sesn2 expression in renal epithelial cells is required to treat CKD, a global health concern, without a viable cure.
Funding
- Other NIH Support