ArticleJournal of neuroinflammation2021
Macrophage-specific RhoA knockout delays Wallerian degeneration after peripheral nerve injury in mice.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- The Effectiveness of Platelet-Rich Plasma in the Treatment of Sciatic Nerve Injury: A Single-Blind Randomized Comparative Trial.Neural plasticity · 2025Trial
- RhoA in postnatal spinal motoneuron is essential for peripheral myelination.Communications biology · 2026Article
- Schwann Cells in Physical Nerve Injury and Tumor Perineural Invasion: A Functional Overview and Comparison.Cancer medicine · 2026Review
- MicroRNA-301a knockout attenuates peripheral nerve regeneration by delaying Wallerian degeneration.Neural regeneration research · 2026Article
- Systemic Inflammation Triggers Motor Axon Degeneration Via Macrophage IL-1β-Mediated P53/SIRT1/Autophagy Pathway.Inflammation · 2026Article
- Ultrasound-guided nanocomposite hydrogel injection to enhance nerve repair via temporal delivery of a colony-stimulating factor 1 receptor inhibitor.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Peptide-Incorporated Biomaterials Promote Regeneration of Peripheral Nerve Injuries.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Research Progress on Spinal Cord Repair Based on Regulation of the Neuroregenerative Microenvironment.Cellular and molecular neurobiology · 2026Review
- Schwann Cell Synthesized Cholesterol Orchestrates Peripheral Nerve Regeneration via Structural and IGF1-Dependent Signaling Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Macrophage-Derived Amphiregulin Enhances Schwann Cell Phagocytosis Through the EGFR/CTSS Signaling Pathway.Molecular neurobiology · 2026Article
- M2 polarization of macrophage induced by IL-33 promotes mouse sciatic nerve regeneration.Cell & bioscience · 2026Article
- Synovial macrophage rhoa protects against osteoarthritis by suppressing YAP/IL-17C mediated chondrocyte senescence.Cell biology and toxicology · 2026Article
- RHOA at the intersection of inflammation-driven and sporadic colorectal cancer.Frontiers in immunology · 2026Review
- Nano-Immunomodulators for Directing Macrophage Fate to Enhance Peripheral Nerve Repair: Advances, Challenges, and Translational Perspectives.International journal of nanomedicine · 2026Review
- Loss of RhoA in microglia disables glycolytic adaptation and impairs spinal cord injury recovery through Arhgap25/HIF-1α pathway.Cell death & disease · 2025Article
- Molecular and cellular mechanisms underlying peripheral nerve injury-induced cellular ecological shifts: Implications for neuroregeneration.IBRO neuroscience reports · 2025Review
- Specific macrophage RhoA targeting CRISPR-Cas9 for mitigating osteoclastogenesis-induced joint damage in inflammatory arthritis.Cell reports. Medicine · 2025Article
- TGF-β1 Improves Nerve Regeneration and Functional Recovery After Sciatic Nerve Injury by Alleviating Inflammation.Biomedicines · 2025Article
- Biomimetic ECM nerve guidance conduit with dynamic 3D interconnected porous network and sustained IGF-1 delivery for enhanced peripheral nerve regeneration and immune modulation.Materials today. Bio · 2025Article
- Protocadherin-7 Regulates Monocyte Migration Through Regulation of Small GTPase RhoA and Rac1.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundPlenty of macrophages are recruited to the injured nerve to play key roles in the immunoreaction and engulf the debris of degenerated axons and myelin during Wallerian degeneration, thus creating a conducive microenvironment for nerve regeneration. Recently, drugs targeting the RhoA pathway have been widely used to promote peripheral axonal regeneration. However, the role of RhoA in macrophage during Wallerian degeneration and nerve regeneration after peripheral nerve injury is still unknown. Herein, we come up with the hypothesis that RhoA might influence Wallerian degeneration and nerve regeneration by affecting the migration and phagocytosis of macrophages after peripheral nerve injury.
methodsImmunohistochemistry, Western blotting, H&E staining, and electrophysiology were performed to access the Wallerian degeneration and axonal regeneration after sciatic nerve transection and crush injury in the Lyz
results1. RhoA was specifically knocked out in macrophages of the cKO mice; 2. The segmentation of axons and myelin, the axonal regeneration, and nerve conduction in the injured nerve were significantly impeded while the myoatrophy was more severe in the cKO mice compared with those in Cre mice; 3. RhoA knockout attenuated the migration and phagocytosis of macrophages in vivo and in vitro; 4. ROCK and MLCK were downregulated in the cKO macrophages while inhibition of ROCK and MLCK could weaken the migration and phagocytosis of macrophages.
conclusionsOur findings suggest that RhoA depletion in macrophages exerts a detrimental effect on Wallerian degeneration and nerve regeneration, which is most likely due to the impaired migration and phagocytosis of macrophages resulted from disrupted RhoA/ROCK/MLCK pathway. Since previous research has proved RhoA inhibition in neurons was favoring for axonal regeneration, the present study reminds us of that the cellular specificity of RhoA-targeted drugs is needed to be considered in the future application for treating peripheral nerve injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.