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ResearchIn-Press PreviewImmunologyNephrology Open Access | 10.1172/jci.insight.186892

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

Zhimin Huang,1 Jiaxin Dong,1 Ziqi Fu,1 Li Li,1 Simeng liu,1 Lin Wu,1 Honglei Guo,1 Ao Bian,1 Kang Liu,1 Wei Sun,2 Changying Xing,1 Steven D. Crowley,3 Jiafa Ren,1 Xiangqing Kong,2 and Huijuan Mao1

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Huang, Z. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Dong, J. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Fu, Z. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Li, L. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by liu, S. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Wu, L. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Guo, H. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Bian, A. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Liu, K. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Sun, W. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Xing, C. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Crowley, S. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Ren, J. in: PubMed | Google Scholar |

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Kong, X. in: PubMed | Google Scholar

1Department of Nephrology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

2Department of Cardiology, Jiangsu Province Hospital and The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

3Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, United States of America

Find articles by Mao, H. in: PubMed | Google Scholar

Published July 29, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.186892.
Copyright © 2025, Huang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 29, 2025 - Version history
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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 (CKD) 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 (IR)-induced tubular injury and renal fibrosis, accompanied by the remarkable downregulation of IL-1R. Transcriptome sequencing showed that LIPUS significantly down-regulated 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 profibrotic cytokines by down-regulating 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 through down-regulating tubular IL-1R.

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