Kidney Week

Abstract: TH-PO0551

Tubular Development and Injury Response of Short-Loop vs. Long-Loop Glomerular Damage in Mice

Session Information

• Development, Stem Cells, and Regenerative Medicine
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

• Liu, Jing, Tongji Hospital Affiliated to Tongji University, Shanghai, China

Jing Liu, MD

• Zhong, Jianyong, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Jianyong Zhong, MD, PhD

• Xiong, Juming, Vanderbilt University, Nashville, Tennessee, United States

Juming Xiong

• Zhu, Yanfan, Vanderbilt University, Nashville, Tennessee, United States

Yanfan Zhu, MS, PhD

• Yue, Jialin, Vanderbilt University, Nashville, Tennessee, United States

Jialin Yue

• Kon, Valentina, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Valentina Kon, MD

• Yu, Chen, Tongji Hospital Affiliated to Tongji University, Shanghai, China

Chen Yu, MD, PhD

• Huo, Yuankai, Vanderbilt University, Nashville, Tennessee, United States

Yuankai Huo, PhD

• Yang, Haichun, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Haichun Yang, MD, PhD

Background

Although the number of glomeruli stabilizes 3 weeks post-birth, kidney size and weight continue growing until week 12, indicating that various tubular segments contribute to maturation. Tubules define distinct nephron populations—short-loop and long-loop glomeruli—though their functions remain unclear. This study evaluates tubule maturation and the impact of early injury on short-loop versus long-loop glomeruli.

Methods

We measured the area of nephron segments, including S1/S2, S3 proximal tubule, descending limb, thin ascending limb, thick ascending limb, distal tubule, and collecting duct, using markers: SGLT2⁺, SGLT2^-/CD13⁺, UT2⁺, CLC⁺, UT2^-/UMOD⁺, NCC⁺, and AQP2⁺. Short-loop glomerular injury was induced in wild-type mice with puromycin (PAN) at birth. Long-loop injury was induced in transgenic mice with LMB2 toxin on day 4 post-birth. Mice then underwent uninephrectomy at week 12 and were exposed to high salt+angiotensin II until sacrificed at week 22 to assess the effects of a secondary injury.

Results

Electrolyte excretion (Na⁺, K⁺, Cl^-, BUN, glucose), a functional indicator related to different tubule segments, displayed a U-shape with four phases during postnatal development (Figure 1). UT2⁺ tubular areas increased from week 0 to 4, while CLC⁺, NCC⁺, and AQP2⁺ areas grew until week 6, then stabilized. In contrast, SGLT2⁺ and SGLT2^-/CD13⁺ areas continued to expand until week 12. Early postnatal injuries induced by both short-loop (PAN) and long-loop (toxin) significantly reduced all biomarkers by week 12. PAN mainly reduced UT2⁺ and NCC⁺ tubules, while LMB2 affected SGLT2^-/CD13⁺ and CLC⁺ tubules. The superimposed second injury caused more severe proximal tubule damage in previously injured long-loop glomeruli (higher urinary KIM-1 levels) compared to normal or PAN-induced short-loop injury.

Conclusion

Proximal tubule maturation spans a longer timeframe compared to other segments. Injury in long-loop glomeruli increases their susceptibility to secondary proximal tubule insults later in life.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025dx6ynn18