Continuous low-intensity ultrasound influences the transcriptomic profile in M1 macrophages by downregulating inflammation and promoting M2-like markers | Scientific Reports
Skip to main content
Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain<br>the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in<br>Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles<br>and JavaScript.
Advertisement
Continuous low-intensity ultrasound influences the transcriptomic profile in M1 macrophages by downregulating inflammation and promoting M2-like markers
Download PDF
Download PDF
Subjects
Biomarkers<br>Computational biology and bioinformatics<br>Diseases<br>Immunology<br>Molecular biology
Abstract<br>Macrophages are key regulators of inflammation, capable of adopting pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes in response to environmental cues. In chronic conditions such as post-traumatic osteoarthritis (PTOA), persistent M1 activation contributes to tissue damage and impaired healing. Traditional models using lipopolysaccharide (LPS) to induce inflammation may not fully capture the complex microenvironment of joint injury. This study employs fibronectin fragments (Fnfs), which are associated with matrix degradation, focusing on establishing a physiologically relevant inflammatory model and applying transcriptomic analysis to investigate how continuous low-intensity ultrasound (cLIUS), a non-pharmacological biophysical stimulus, modulates macrophage responses under Fnfs-induced conditions. Beyond identifying differentially expressed genes (DEGs), we introduce differential clustering (DC) to capture transcriptional remodeling, revealing coordinated co-expression shifts overlooked by gene-level analyses. Two modes in the DC analysis, namely same-different (SD) and different-same (DS), capture both canonical and non-canonical M2-associated genes, with only partial overlap between their ranked gene lists, as quantified by concordance indices of 0.52 for SD genes and 0.42 for DS genes (scale 0–1). These findings suggest that cLIUS shifts Fnfs-induced macrophages toward an M2-like reparative phenotype. The coordinated shifts in expression captured by DC complement standard differential expression, providing a perspective on how biophysical treatments such as cLIUS modulate immune cell behavior.
Similar content being viewed by others
A 2D inflammatory co-culture model for investigating synovial fibroblast and macrophage interactions in rheumatoid arthritis
Article<br>Open access<br>17 August 2025
Large-scale computational modelling of the M1 and M2 synovial macrophages in rheumatoid arthritis
Article<br>Open access<br>26 January 2024
Dynamic macrophage phenotypes in autoimmune and inflammatory rheumatic diseases
Article
28 July 2025
Funding<br>This work is supported by the U.S. National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 Grant No. 1R01AR079499-01A1; Funder ID: https://doi.org/10.13039/100000069).
Author information<br>Authors and Affiliations<br>Department of Biological Sciences, Biotechnology Graduate Program, Shelby Science and Technology, University of Alabama-Huntsville, 35899-0643, AL, Alabama-Huntsville, USA<br>Shahid Khan
Department of Chemical and Materials Engineering, University of Alabama-Huntsville, 117-J Engineering Building, 35899-0643, AL, Alabama-Huntsville, USA<br>Owen Trippany & Anuradha Subramanian
Department of Mathematical Sciences, University of Alabama-Huntsville, 35899-0643, AL, Alabama-Huntsville, USA<br>Satyaki Roy
AuthorsShahid KhanView author publications<br>Search author on:PubMed Google Scholar
Owen TrippanyView author publications<br>Search author on:PubMed Google Scholar
Anuradha SubramanianView author publications<br>Search author on:PubMed Google Scholar
Satyaki RoyView author publications<br>Search author on:PubMed Google Scholar
Corresponding author<br>Correspondence to<br>Satyaki Roy.
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information<br>Publisher’s note<br>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.<br>Supplementary Material 1 (download DOCX )
Supplementary Material 2 (download DOCX )
Supplementary Material 3 (download XLSX )
Supplementary Material 4 (download XLSX )
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the...