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

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]. Funding: Government Support – Non-U.S.1.LIPUS treating renal fibrosis through inhibition of tubular IL-1R2. A diagram of the molecular mechanism of LIPUS treatment in renal fibrosis