Abstract: TH-PO904
Dicer Deficiency in Proximal Tubules Exacerbates Renal Injury and Tubulointerstitial Fibrosis in Diabetes and UUO Models by Upregulating Smad2/3 Expression
Session Information
- Molecular Mechanisms of CKD - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Ma, Zhengwei, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
- Wei, Qingqing, Medical College of Georgia, Augusta University, Augusta, Georgia, United States
- Dong, Zheng, Medical College of Georgia, Augusta, Georgia, United States
Group or Team Name
- Augusta University
Background
Renal fibrosis is a common pathological feature in chronic kidney disease, including diabetic kidney disease (DKD) and obstructive nephropathy. Multiple microRNA species have been implicated in the pathogenesis of both DKD and obstructive nephropathy. Dicer is a key RNase III enzyme for microRNA biogenesis, which has been shown to play an important role in kidney development and renal ischemia-reperfusion injury. However, the role of Dicer in diabetic and obstructive kidney diseases remain unclear.
Methods
Dicer was specifically ablated from Kidney proximal tubules in mice by breeding Dicer-floxed mice with PEPCK-Cre mice. Proximal tubule Dicer knockout (PT-Dicer-KO) mice and wild-type (WT) mice were subjected to STZ treatment to induce DKD or unilateral urethral obstruction (UUO) to examine renal hypertrophy, renal injury and fibrosis.
Results
We found that Dicer-KO in proximal tubules deteriorated renal interstitial inflammation, tubular injury, and tubolointerstitial fibrosis without significantly affecing renal hypertrophy following STZ treatment. Dicer-KO exacerbated renal injury and tubolointerstitial fibrosis in the UUO model as well. At the molecular level, Dicer deficiency induced Smad2/3 expression in proximal tubules, which may contribute to the enhanced tubolointerstitial fibrosis in both STZ-diabetes and UUO models.
Conclusion
Our results provide further support for the regulatory role of Dicer and associated microRNA production in the development of chronic renal pathologies in DKD and obstructive nephropathy. Dicer deficiency may up-regulate Smad2/3 and increase renal apoptosis to enhance the progression of chronic kidney disease.
Funding
- NIDDK Support