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-PO615

PTEN Deletion in the Bladder Superficial Epithelium and Kidney Tubules Enhances Bacterial Burden During Urinary Tract Infections

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

  • Bochter, M. Skye N., Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
  • Bender, Kristin, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
  • Schwartz, Laura, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
  • Spencer, John David, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
Background

Urinary tract infections (UTI) are one of the most common types of bacterial infections, affecting more than 150 million individuals a year. Previous work from our lab identified a role for PI3K/AKT signaling regulating in the innate immune response in the bladder and kidneys. To further investigate the significance of PI3K/AKT signaling on host defense, we genetically deleted Pten, a PI3K/AKT antagonist, in the superficial cells of the bladder urothelium or in the epithelium of the distal nephron and collecting ducts of the kidney.

Methods

Mice homozygous for the floxed Pten gene were crossed with transgenic mice expressing the Cre recombinase under the control of the Uroplakin2 (Upk2) promoter or cadherin 16 (KSP) promoter to create bladder urothelium-specific or kidney tubule-specific Pten knockout (PTEN-KO) mice. PTEN-KO mice and Cre-negative littermate controls (PTENflox) were transurethrally infected with uropathogenic E. coli. At 16 and 24hrs post infection, E. coli burden was quantified in the urine, bladder, and kidney.

Results

Upk2-Cre and KSP-Cre PTEN-KO mice showed normal phenotypes and development. PCR confirmed Cre-recombination in PTEN-KO bladders and kidneys. qRT-PCR confirmed Pten mRNA deletion. Compared to PTENflox littermate controls, bladder and kidney tissue from Upk2-Cre and KSP-Cre PTEN-KO mice appeared phenotypically normal by light microscopy.
Following experimental UTI, Upk2-Cre and KSP-Cre PTEN-KO mice had 1-1.5-fold greater urine and bladder bacterial burden at both 16 and 48hpi compared to PTENflox control mice.

Conclusion

These results indicate that PI3K/AKT signaling in the bladder urothelium and kidney tubules impacts UTI susceptibility. They provided added support that the kidney tubules contribute to UTI defense. Additional studies are needed to identify the mechanisms of how PI3K/AKT signaling regulates host defenses and how PI3K/AKT hyper-activation enhances UTI susceptibility.

Funding

  • NIDDK Support