ArticleExperimental & molecular medicine2021
WISP-1 induced by mechanical stress contributes to fibrosis and hypertrophy of the ligamentum flavum through Hedgehog-Gli1 signaling.
Article in Experimental & molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Mechanobiology of Matricellular Proteins in Bladder Cancer: A Narrative Review and Bioinformatics Analysis.Biomolecules · 2026Review
- Pirfenidone attenuates urethral stricture after injury by inhibiting Gli2 mediated HAS2 expression in fibroblasts.Journal of molecular histology · 2026Article
- Cartilage intermediate layer protein inhibits ligamentum flavum hypertrophy mediated by TGF-β1/SMAD3/SERPINE2 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Placental alkaline phosphatase promotes lipid accumulation and fibrosis in ligamentum flavum hypertrophy and represents a potential target for statin repurposing.Frontiers in pharmacology · 2026Article
- From mechanotransduction to manual therapy: advances in piezo/TRP channels and lumbar degeneration.Frontiers in physiology · 2026Review
- Single-cell multi-omics analysis identifies SPP1Biomarker research · 2025Article
- Single-cell RNA-seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy.Frontiers in immunology · 2025Article
- Mechanical stress contributes to ligamentum flavum hypertrophy by inducing local inflammation and myofibroblast transition in the innovative surgical rabbit model.Frontiers in immunology · 2025Article
- Animal Models of Intervertebral Disc Diseases: Advantages, Limitations, and Future Directions.Neurology international · 2024Review
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Cellular and Molecular Mechanisms of Hypertrophy of Ligamentum Flavum.Biomolecules · 2024Review
- WISP1 and Macrophage Migration Inhibitory Factor in Respiratory Inflammation: Novel Insights and Therapeutic Potentials for Asthma and COPD.International journal of molecular sciences · 2024Review
- RMRP accelerates ligamentum flavum hypertrophy by regulating GSDMD-mediated pyroptosis through Gli1 SUMOylation.Frontiers in immunology · 2024Article
- M2 macrophages mediate fibrotic scar formation in the early stages after cerebral ischemia in rats.Neural regeneration research · 2023Article
- Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Decorin: a potential therapeutic candidate for ligamentum flavum hypertrophy by antagonizing TGF-β1.Experimental & molecular medicine · 2023Article
- Article
- TCF7/SNAI2/miR-4306 feedback loop promotes hypertrophy of ligamentum flavum.Journal of translational medicine · 2022Article
- The Effects of Hedgehog Signaling Pathway on the Proliferation and Apoptosis of Melanoma Cells.Journal of oncology · 2022Article
- Characterization of ligamentum flavum hypertrophy based on m6A RNA methylation modification and the immune microenvironment.American journal of translational research · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ongoing chronic fibrosis and hypertrophy of the ligamentum flavum (LF) is an important cause of lumbar spinal canal stenosis (LSCS). Our previous work showed that WNT1-inducible signaling pathway protein 1 (WISP-1) is a critical driver of LF fibrosis. However, the potential mechanism has not been explored. Here, we found that Gli1 was upregulated in hypertrophic LF tissues and required for fibrogenesis in fibroblasts. Moreover, mechanical stretching increased the expression of WISP-1 in LF fibroblasts. Furthermore, WISP-1 induced fibrogenesis in vitro through the Hedgehog-Gli1 pathway. This conclusion was supported by the fact that WISP-1 activated the Hedgehog-Gli1 pathway in LF fibroblasts and that cyclopamine attenuated the effect of WISP-1-induced fibrogenesis. WISP-1 also promoted the transition of fibroblasts into myofibroblasts via the Hedgehog pathway. Importantly, a hypertrophic LF rabbit model induced by mechanical stress also showed pathological changes in fibrosis and elevated expression of WISP-1, Gli1, and α-SMA. Therapeutic administration of cyclopamine reduced collagen expression, fibroblast proliferation, and myofibroblast differentiation and ameliorated fibrosis in the mechanical stress-induced rabbit model. Collectively, our findings show mechanical stress/WISP-1/Hedgehog signaling as a new fibrotic axis contributing to LF hypertrophy and identify Hedgehog signaling as a therapeutic target for the prevention and treatment of LF fibrosis.
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