Low-intensity pulsed ultrasound stimulation to treat renal fibrosis through inhibiting tubular IL-1R.

Abstract

Low-intensity pulsed ultrasound stimulation (LIPUS) has become increasingly appreciated for its therapeutic effect on kidney diseases. However, its role and biological mechanism in treating chronic kidney disease remain poorly defined. Here, we revealed that LIPUS was applied in a safe range with an intensity of 25-315 mW/cm2. Daily LIPUS at an intensity of 315 mW/cm2 ameliorated ischemia/reperfusion-induced (IR-induced) tubular injury and renal fibrosis, accompanied by the remarkable downregulation of IL-1R. Transcriptome sequencing showed that LIPUS significantly downregulated IL-1R and its downstream genes in IL-1β-stimulated IR-injured mice. LIPUS effectively reversed IL-1β-induced tubular injury and reduced the production of pro-fibrotic cytokines by downregulating IL-1R in vivo and in vitro. Renal proximal tubule-specific Il1r1-knockout mice exhibited milder renal tubular injury and fibrosis after IR injury. However, LIPUS did not ameliorate IR injury in proximal tubule-specific Il1r1-knockout mice. Collectively, daily LIPUS at an intensity of 315 mW/cm2 relieves IR-induced tubular injury and fibrosis, potentially by downregulating tubular IL-1R.