ArticleExperimental & molecular medicine2022
Clusterin negatively modulates mechanical stress-mediated ligamentum flavum hypertrophy through TGF-β1 signaling.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07026552 (Proteomic and Histological Analysis of Ligamentum Flavum Hypertrophy and Degeneration in Lumbar Spinal Stenosis), which is not on this map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Proteomic and Histological Analysis of Ligamentum Flavum Hypertrophy and Degeneration in Lumbar Spinal Stenosis: Clinical, Surgical, and Therapeutic Implications
Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- SnoN Is Involved in Regulation of the TGFβ/Smad Signaling Pathway in Patients with Degenerative Lumbar Canal Stenosis.Neurologia medico-chirurgica · 2026Article
- The Main Immune Markers of Ligamentum Flavum Hypertrophy: A Narrative Literature Review.International journal of molecular sciences · 2026Review
- Role of Klhl14 in senescence and epithelial-to-mesenchymal transition via TGF-β modulation.Cell death & disease · 2026Article
- Cartilage intermediate layer protein inhibits ligamentum flavum hypertrophy mediated by TGF-β1/SMAD3/SERPINE2 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- The protection of mesenchymal stem cells in metabolic reprogramming and endothelial-mesenchymal transition in diabetic aortas.Stem cells translational medicine · 2026Article
- Construction and Validation of a Nomogram Prediction Model for Recurrent Lumbar Disc Herniation After Percutaneous Endoscopic Lumbar Discectomy.Risk management and healthcare policy · 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
- Epigenetic modification regulates the ligamentum flavum hypertrophy through miR-335-3p/SERPINE2/β-catenin signaling pathway.Cellular & molecular biology letters · 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
- Elucidating the function of clusterin in the progression of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- Ligamentum flavum hypertrophy animal models: methodological trade-offs and future directions.Frontiers in veterinary science · 2025Article
- Cellular and Molecular Mechanisms of Hypertrophy of Ligamentum Flavum.Biomolecules · 2024Review
- Profibrotic role of transcription factor SP1 in cross-talk between fibroblasts and M2 macrophages.iScience · 2023Article
- Astrocyte senescence-like response related to peripheral nerve injury-induced neuropathic pain.Cellular & molecular biology letters · 2023Article
- Decorin: a potential therapeutic candidate for ligamentum flavum hypertrophy by antagonizing TGF-β1.Experimental & molecular medicine · 2023Article
- Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligamentum flavum hypertrophy (LFH) is a major cause of lumbar spinal canal stenosis (LSCS). The pathomechanisms for LFH have not been fully elucidated. Isobaric tags for relative and absolute quantitation (iTRAQ) technology, proteomics assessments of human ligamentum flavum (LF), and successive assays were performed to explore the effect of clusterin (CLU) upregulation on LFH pathogenesis. LFH samples exhibited higher cell positive rates of the CLU, TGF-β1, α-SMA, ALK5 and p-SMAD3 proteins than non-LFH samples. Mechanical stress and TGF-β1 initiated CLU expression in LF cells. Notably, CLU inhibited the expression of mechanical stress-stimulated and TGF-β1-stimulated COL1A2 and α-SMA. Mechanistic studies showed that CLU inhibited mechanical stress-stimulated and TGF-β1-induced SMAD3 activities through suppression of the phosphorylation of SMAD3 and by inhibiting its nuclear translocation by competitively binding to ALK5. PRKD3 stabilized CLU protein by inhibiting lysosomal distribution and degradation of CLU. CLU attenuated mechanical stress-induced LFH in vivo. In summary, the findings showed that CLU attenuates mechanical stress-induced LFH by modulating the TGF-β1 pathways in vitro and in vivo. These findings imply that CLU is induced by mechanical stress and TGF-β1 and inhibits LF fibrotic responses via negative feedback regulation of the TGF-β1 pathway. These findings indicate that CLU is a potential treatment target for LFH.
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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.