Kidney Week

Abstract: SA-PO1187

Low-Intensity Pulsed Ultrasound Stimulation to Treat Kidney Fibrosis through Inhibition of Tubular IL-1R

Session Information

• CKD: Mechanisms - 3
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Huang, Zhimin, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Zhimin Huang

• Dong, Jiaxin, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Jiaxin Dong, MD

• Fu, Ziqi, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Ziqi Fu

• Ren, Jiafa, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Jiafa Ren, MD, PhD

• Mao, Huijuan, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Huijuan Mao, MD, PhD

Background

Low intensity pulsed ultrasound (LIPUS) has become increasingly appreciated for kidney diseases. However, its mechanisms for chronic kidney disease (CKD) remain poorly defined.

Methods

Under different parameters of LIPUS, histological tests and molecular biology were determined. We detected IL-1β/IL-1R and its downstream in unilateral renal ischemia/reperfusion (IR) induced renal fibrosis and IL-1β-induced tubular partial epithelial-to-mesenchymal transition with or without LIPUS treatment. In addition, we evaluated the IL-1R dependence of LIPUS in treating IR-induced CKD models using tubular IL-1R^-/- mice.

Results

Daily LIPUS treatment at 315 mW/cm² reduced the IR-induced tubular injury and fibrosis, accompanied by the remarkable amelioration in IL-1β and IL-1R[Fig.1A-D]. Transcriptome sequencing showed a significant reduction of IL-1R and its downstream(p-NF-κB, Myc) in the LIPUS-treated IR-injured plus IL-1β stimulation, compared to the untreated diseased group[Fig.1E-G]. LIPUS treatment reversed IL-1β induced tubular injury and profibrotic cytokines by reducing IL-1R in vivo and in vitro. Knockout mice lacking tubular IL-1R expression exhibited less renal tubular injury and retained a more preserved renal function after IR injury. However, LIPUS treatment showed no more improvement in tubular IL-1R Knockout mice after IR injury[Fig.1H-J].

Conclusion

Daily LIPUS treatment at 315 mW/cm² could reduce IR-induced tubular injury and fibrosis by ameliorating tubular IL-1R[Fig.2].

1.LIPUS treating renal fibrosis through inhibition of tubular IL-1R

2. A diagram of the molecular mechanism of LIPUS treatment in renal fibrosis

Funding

• Government Support – Non-U.S.