Kidney Week

Abstract: SA-PO0132

Role of Glutamine Transport in Cystic Epithelial Cells in Kidney Cystogenesis in Tuberous Sclerosis Complex Mouse Models

Session Information

• ADPKD and Cystic Kidney Disease - 3
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Barone, Sharon L., New Mexico VA Health Care System, Albuquerque, New Mexico, United States

Sharon L. Barone, MS

• Zahedi, Kamyar A., New Mexico VA Health Care System, Albuquerque, New Mexico, United States

Kamyar A. Zahedi, PhD

• Brooks, Marybeth, New Mexico VA Health Care System, Albuquerque, New Mexico, United States

Marybeth Brooks

• Tolino, Hozhoni E., The University of New Mexico School of Medicine, Albuquerque, New Mexico, United States

Hozhoni E. Tolino

• In, Julie Goeun, The University of New Mexico School of Medicine, Albuquerque, New Mexico, United States

Julie Goeun In, PhD

• Soleimani, Manoocher, New Mexico VA Health Care System, Albuquerque, New Mexico, United States

Manoocher Soleimani, MD

Background

The epithelium of renal cysts in Tuberous Sclerosis Complex (TSC) is primarily comprised of proliferating A-intercalated cells (A-ICs) that, like other mitotically active cells, rely on energy and nutrients for survival and growth.

Methods

RNA-seq and expression studies were used to characterize and localize the expression of differentially expressed glutamine-dependent transporters in the kidneys of TSC mouse models.

Results

STAT3 and Hypoxia-inducible Factor 1a (Hif1a), as well as c-MYC, which play critical roles in activating glutaminolysis in various kidney tumors, are robustly upregulated and detected in the nuclei of cyst epithelial cells. Our results also show the robust upregulation of Na-glutamine co-transporters Slc38a1, Slc38a2, and Slc38a3, and the glutamine transporter Slc1a5 to the epithelium of TSC renal cysts. A crucial finding is the induction of the Na-Glutamine cotransporter SLC38A3 and its localization to the basolateral membrane of cystic A-IC cells. These changes are accompanied by increased expression of the cytosolic enzyme GLS2, which facilitates the breakdown of glutamine to glutamate and NH₃, and GLUL. The two main NH₃ transporters, Rhcg and Rhbg, are robustly upregulated in A-IC cells lining the cysts. Lastly, we demonstrated that feeding Tsc1KO mice a glutamine-deficient diet for 22 days significantly reduced the kidney cyst burden.

Conclusion

Our results suggest that STAT3, HIF1a, and c-MYC play critical roles in upregulating glutaminolysis (e.g., glutamine transporters and metabolism), which is critical to the proliferation and expansion of TSC renal cysts. Understanding the intricate interplay among these metabolic pathways will provide opportunities to develop novel therapies for kidney cystogenesis in TSC.

Funding

• Other NIH Support