# LIPUS as a potential strategy for anti-inflammation and repair: A review of the mechanisms

**Authors:** Gaocheng Wang, Jianping Zhao, Jiaxuan Li, Zhanguo Zhang, Wanguang Zhang, Qian Chen, Jingjing Wang

PMC · DOI: 10.7150/ijms.124996 · 2026-02-18

## TL;DR

This paper reviews how low-intensity pulsed ultrasound (LIPUS) can help reduce inflammation and promote tissue repair in various diseases.

## Contribution

The paper compiles and analyzes the molecular mechanisms and clinical evidence supporting LIPUS as a non-invasive therapy for inflammation and tissue repair.

## Key findings

- LIPUS has demonstrated anti-inflammatory effects in both clinical and preclinical studies.
- LIPUS promotes tissue repair and regeneration through various molecular pathways.
- Clinical trials suggest LIPUS can aid in restoring organ function after inflammation.

## Abstract

Hundreds of millions of people worldwide endure continuous suffering and significant economic burdens due to inflammatory diseases. Various acute and chronic inflammatory diseases and the natural aging of the human body are common causes of organ damage. Therefore, how to reasonably regulate inflammation, tissue repair and regeneration after organ damage has been of great concern, especially the pathological repair caused by inflammation will lead to the destruction of the original structure and function of tissues and organs. Low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive physical therapy that can produce different biological effects on organs, tissues and cells. Certain clinical trials have demonstrated the outstanding capacity of LIPUS in anti-inflammation and repair. Many in vivo and in vitro basic studies have also reported the molecular effect mechanisms by which LIPUS exerts capacity of anti-inflammation and repair. This review focuses on the molecular mechanism of LIPUS anti-inflammation and repair and emphasizes the crucial role of LIPUS in various diseases. In addition, we compile clinical trials to provide readers with a more thorough understanding of the current potential of LIPUS in inflammation control and organ function restoration.

## Full-text entities

- **Genes:** Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Junb (jun B proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16477], Il1a (interleukin 1 alpha) [NCBI Gene 24493] {aka IL-1 alpha, IL-1F1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, TNFAIP3 (TNF alpha induced protein 3) [NCBI Gene 7128] {aka A20, AIFBL1, AISBL, OTUD7C, TNFA1P2}, NTRK2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 4915] {aka DEE58, EIEE58, GP145-TrkB, OBHD, TRKB, trk-B}, Ptk2 (PTK2 protein tyrosine kinase 2) [NCBI Gene 14083] {aka FADK 1, FAK, FRNK, Fadk, p125FAK}, MUL1 (mitochondrial E3 ubiquitin protein ligase 1) [NCBI Gene 79594] {aka C1orf166, GIDE, MAPL, MULAN, RNF218}, Fzd5 (frizzled class receptor 5) [NCBI Gene 317674], TRPV4 (transient receptor potential cation channel subfamily V member 4) [NCBI Gene 59341] {aka BCYM3, CMT2C, HMSN2C, OTRPC4, SMAL, SPSMA}, Smad3 (SMAD family member 3) [NCBI Gene 25631] {aka Madh3, Smad 3, mad3}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, Bdnf (brain-derived neurotrophic factor) [NCBI Gene 24225], Ctnnb1 (catenin beta 1) [NCBI Gene 84353] {aka Catnb}, DNMT3A (DNA methyltransferase 3 alpha) [NCBI Gene 1788] {aka DNMT3A2, HESJAS, M.HsaIIIA, TBRS}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, IFT88 (intraflagellar transport 88) [NCBI Gene 8100] {aka D13S1056E, DAF19, TG737, TTC10, hTg737}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, Mir16-1 (microRNA 16-1) [NCBI Gene 387134] {aka Mirn16, Mirn16-1, miR-16, mir-16-1}, CCL1 (C-C motif chemokine ligand 1) [NCBI Gene 6346] {aka I-309, P500, SCYA1, SISe, TCA3}, EPHB4 (EPH receptor B4) [NCBI Gene 2050] {aka CMAVM2, HFASD, HTK, LMPHM7, MYK1, TYRO11}, Nox4 (NADPH oxidase 4) [NCBI Gene 50490], Ephb1 (Eph receptor B1) [NCBI Gene 24338] {aka Ephb2, Erk, elk}, Crmp1 (collapsin response mediator protein 1) [NCBI Gene 12933] {aka CRMP-1, DRP-1, Dpysl1, ULIP-3, Ulip3}, Mir21a (microRNA 21a) [NCBI Gene 387140] {aka Mir21, Mirn21, mmu-mir-21, mmu-mir-21a}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TRPM7 (transient receptor potential cation channel subfamily M member 7) [NCBI Gene 54822] {aka ALSPDC, CHAK, CHAK1, LTRPC7, LTrpC-7, TRP-PLIK}, Ntrk2 (neurotrophic receptor tyrosine kinase 2) [NCBI Gene 25054] {aka RATTRKB1, TRKB1, Tkrb, trk-B, trkB}, Chrna7 (cholinergic receptor, nicotinic, alpha polypeptide 7) [NCBI Gene 11441] {aka Acra7, alpha7, nAChR7, nAchR}, KCNK4 (potassium two pore domain channel subfamily K member 4) [NCBI Gene 50801] {aka FHEIG, K2p4.1, TRAAK, TRAAK1}, CAMK2G (calcium/calmodulin dependent protein kinase II gamma) [NCBI Gene 818] {aka CAMK, CAMK-II, CAMKG, MRD59}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, Pik3cg (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma) [NCBI Gene 298947] {aka Pi3k}, STAT6 (signal transducer and activator of transcription 6) [NCBI Gene 6778] {aka D12S1644, HIES6, IL-4-STAT, STAT6B, STAT6C}, NGF (nerve growth factor) [NCBI Gene 4803] {aka Beta-NGF, HSAN5, NGFB}, OSM (oncostatin M) [NCBI Gene 5008], RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, MAP3K5 (mitogen-activated protein kinase kinase kinase 5) [NCBI Gene 4217] {aka ASK1, MAPKKK5, MEKK5}, Yap1 (yes-associated protein 1) [NCBI Gene 22601] {aka Yap, Yap65, Yki, Yorkie}, Agtr1b (angiotensin II receptor, type 1b) [NCBI Gene 81638] {aka AT1, AT1B, AT3, AT<sub>1</sub>R, Agtr1}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, FBXL2 (F-box and leucine rich repeat protein 2) [NCBI Gene 25827] {aka FBL2, FBL3}, Kif5b (kinesin family member 5B) [NCBI Gene 16573] {aka Khc, Khcs, Kns1, Ukhc}, MIR140 (microRNA 140) [NCBI Gene 406932] {aka MIRN140, SEDN, miRNA140, mir-140}, Piezo1 (piezo-type mechanosensitive ion channel component 1) [NCBI Gene 234839] {aka 9630020g22, Fam38a, mKIAA0233}, Epas1 (endothelial PAS domain protein 1) [NCBI Gene 29452] {aka HIF-2 alpha, HIF2 alpha, HLF, Hif2a}
- **Diseases:** hypoxic (MESH:D002534), ventricular arrhythmias (MESH:D001145), mandibular fractures (MESH:D008337), refractory angina (MESH:D000069279), lung inflammation (MESH:D011014), immune-mediated inflammatory diseases (MESH:C567355), myocarditis (MESH:D009205), OA (MESH:D010003), arthritic (MESH:D015535), ischemia (MESH:D007511), fibular fracture (MESH:D020427), acute (MESH:D000208), temporomandibular disorders (MESH:D013705), CAP (MESH:C535672), NP (MESH:C537927), chondrocyte damage (MESH:D020263), PTOA (MESH:D004834), hypoxia (MESH:D000860), cartilage destruction (MESH:D002357), Chronic inflammation (MESH:D007249), cardiomyocyte injury (MESH:D014947), degenerative (MESH:D019636), cardiac fibrosis (MESH:D005355), Bone fracture (MESH:D050723), Peripheral nerves injury (MESH:D059348), pain (MESH:D010146), mitochondrial dysfunction (MESH:D028361), Muscle and (MESH:D019042), PD (MESH:D010300), cancer (MESH:D009369), acute and chronic inflammatory diseases (MESH:D020275), diabetic (MESH:D003920), cirrhosis of the liver (MESH:D008103), TBI (MESH:D000070642), neuroinflammation (MESH:D000090862), Buerger's disease (MESH:D013919), emphysema (MESH:D004646), chronic kidney disease (MESH:D051436), chronic sleep deprivation (MESH:D012892), Kidney injury (MESH:D007674), heart failure (MESH:D006333), organ damage (MESH:D000092124), rotator cuff (MESH:D000070636), muscle injury (MESH:D009135), LIPUS (MESH:D009800), pulmonary fibrosis (MESH:D011658), periodontal tissue damage (MESH:D010510), tissue injury (MESH:D017695), Chronic Prostatitis Symptom (MESH:D011472), Chronic inflammatory diseases (MESH:D002908), neuro-related disorders (MESH:C536203), glomerulosclerosis (MESH:D005921), MI/R (MESH:D015427), cerebral gliosis (MESH:D005911), RA (MESH:D001172), death (MESH:D003643), BCNI (MESH:D000071576), transverse aortic constriction (MESH:D009188), Brain damage and dysfunction (MESH:D001927), muscle and tendon injuries (MESH:D013708)
- **Chemicals:** ACh (MESH:D000109), NE (MESH:D009638), GABA (MESH:D005680), nitric oxide (MESH:D009569), oxygen (MESH:D010100), ATP (MESH:D000255), steroids (MESH:D013256), LPS (MESH:D008070), calcium (MESH:D002118), ROS (MESH:D017382), Ca2+ (-), potassium (MESH:D011188), adriamycin (MESH:D004317), nitroglycerin (MESH:D005996), phosphatidylcholine (MESH:D010713), L-arginine (MESH:D001120)
- **Species:** Veillonella (genus) [taxon 29465], Mus musculus (house mouse, species) [taxon 10090], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Ureaplasma (genus) [taxon 2129], Methyloversatilis (genus) [taxon 378210], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), MC3T3-E1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0409)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965064/full.md

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Source: https://tomesphere.com/paper/PMC12965064