ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO613

Distinct miRNA Profiles Govern the Host Response to Bacterial Cystitis vs. Pyelonephritis

Session Information

  • Pediatric Nephrology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Ballash, Gregory, Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Li, Birong, Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Cortado, Hanna H., Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Cotzomi Ortega, Israel, Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Jackson, Ashley R., Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Ruiz-Rosado, Juan de Dios, Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Becknell, Brian, Kidney and Urinary Tract Center, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, United States

Group or Team Name

  • Kidney and Urinary Tract Center
Background

Urinary tract infections (UTIs) are one of the most common bacterial infections of childhood. The innate immune response is essential for pathogen detection and eradication, but excessive inflammation can result in urothelial remodeling that increase risk of subsequent infection and long-term sequelae. MicroRNA are small, non-coding RNA with key roles in regulating renal inflammation and tissue remodeling, but their expression and function in UTI are unknown. Here we investigate miRNA dynamics in the setting of experimental cystitis and pyelonephritis.

Methods

Female C3H/HeOuJ mice underwent transurethral inoculation with uropathogenic Escherichia coli (UPEC) or carrier. Bladders and kidneys were harvested 7 days post infection for miRNA and total RNA sequencing. Transcriptome analysis was performed using GO and Ingenuity. Differential miR expression was validated by QPCR. In certain experiments, miR expression was measured in purified urothelial cells following fluorescence activated cell sorting. The kinetics of miR expression elicited by UPEC was studied in immortalized human urothelial cells.

Results

The kidney and bladder miRome varied markedly in response to UPEC infection, with renal miR regulating the proliferative/regenerative response, while bladder miR regulated inflammation and a Tlr4/NF-kB response to Gram-negative bacteria. QPCR validated upregulation of miR-155, -146a, and miR-21, and pathway analysis identified these miR as significant upstream regulators of mRNA expression during cystitis. We determined that a subset of miR were expressed by Upk2+ urothelial cells, and that miR-146a levels increased within this population following UPEC infection. A similar induction of miR-146a occurred in human urothelial cells following UPEC treatment in vitro.

Conclusion

Distinct miRNA are induced by UPEC during cystitis and pyelonephritis. In the bladder, the targetome of miR-155, miR-146a, and miR-21 suggests their regulatory role in reducing inflammation. Complementary studies in isolated urothelial cells establish this lineage as a source of UPEC-elicited miR in vivo and in vitro. These observations justify further studies to identify the functional significance and mechanistic properties of miRNA during UTI.

Funding

  • NIDDK Support