Abstract: FR-PO701
MicroRNA 146a Is a Negative Regulator of the Host Innate Immune Response to Urinary Tract Infection
Session Information
- Pediatric Nephrology - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Li, Birong, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
- Kercsmar, Macie M., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
- Cortado, Hanna H., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
- Becknell, Brian, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
Background
Urinary tract infections (UTIs) rank among the most common bacterial infections in children and adults. The innate immune response is essential for pathogen detection and eradication during UTI, but excessive inflammation can lead to renal injury and scarring. MicroRNA (miR) are small, non-coding RNA with key roles in regulating renal inflammation and tissue remodeling, but their expression and function in UTI are unknown. We investigated miR dynamics and the specific role of miR146a in the setting of experimental cystitis.
Methods
Female C57BL/6J mice underwent transurethral inoculation with uropathogenic Escherichia coli (UPEC). Bladders were harvested 7 days post infection for miR and total RNA sequencing. Transcriptome analysis was performed using GO and Ingenuity. Differential miR expression was validated by QRT-PCR during experimental cystitis. miR146a deficient and control mice were challenged with experimental UTI to investigate differences in susceptibility.
Results
UPEC infection led to dynamic changes in the bladder miRome, and miR146a was identified as the miR with the greatest fold-change. QRT-PCR validated induction of miR146a, and analysis of the predicted targets of miR-146a suggest its regulatory role in reducing inflammation. Mice with global miR146a deficiency were more susceptible to experimental UTI.
Conclusion
MiR146a is a negative regulator of the host innate immune response during UTI. Further studies are justified to identify the direct targets of miR146a and the therapeutic impact of miR146a mimetics during UTI.