Kidney Week

Abstract: TH-PO0042

Effects of Pharmacological Piezo1 Activation on Renal KLHL3-WNK Signaling In Vivo

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic Research
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Ishizawa, Kenichi, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

Kenichi Ishizawa, MD, PhD

• Kaseda, Ken, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

Ken Kaseda, MD

• Tomomitsu, Yoshihiro, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

Yoshihiro Tomomitsu, MD

• Hirohama, Daigoro, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

Daigoro Hirohama, MD, PhD

• Yamazaki, Osamu, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

Osamu Yamazaki, MD, PhD

• Shibata, Shigeru, Teikyo University School of Medicine, Itabashi, Tokyo, Japan

Shigeru Shibata, MD, PhD, FASN

Background

Mechanosensitive signaling has emerged as an important regulator of systemic electrolyte homeostasis. Kelch-like 3 (KLHL3) is a component of an E3 ubiquitin ligase complex that binds to and degrades with-no-lysine kinases (WNKs) in the kidney. In our recent study, we demonstrated that the mechanosensor Piezo1 regulates potassium balance through KLHL3-dependent modulation of WNK signaling in erythrocytes and in the kidney (Ishizawa et al. PNAS 2026). Whether pharmacologic activation of Piezo1 alters renal WNK signaling in vivo in the kidney remains unclear.

Methods

C57/BL6J mice received intraperitoneal administration of Yoda1, a Piezo1 agonist, or a vehicle control (n=8). Yoda1 was dissolved in DMSO and diluted in PBS, and the vehicle control consisted of the same DMSO/PBS mixture. Renal expression of WNK pathway components, such as WNK1, WNK4, and phosphorylated KLHL3 were evaluated by Western blot analysis.

Results

Compared with vehicle-treated mice, Yoda1-treated mice showed significantly reduced levels of phosphorylated KLHL3 in the kidney. Moreover, we found that renal WNK1 and WNK4 levels were also reduced following Yoda1 treatment. These findings indicate that systemic pharmacologic activation of Piezo1 suppresses renal WNK signaling in vivo.

Conclusion

These data extend our previous findings and further support a role for the Piezo1–KLHL3–WNK signaling axis in systemic potassium homeostasis.