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http://purl.uniprot.org/citations/33637374http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33637374http://www.w3.org/2000/01/rdf-schema#comment"

Background

Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures.

Methods

We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-β1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-β1-induced myofibroblast differentiation and fibrosis.

Results

Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-β1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-β1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells.

Conclusion

FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-β1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.org/dc/terms/identifier"doi:10.1016/j.jos.2021.01.004"xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Hayashi K."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Nakamura H."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Suzuki A."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Hori Y."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Terai H."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Salimi H."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Habibi H."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Orita K."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/author"Yabu A."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/name"J Orthop Sci"xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/pages"299-307"xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/title"Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis."xsd:string
http://purl.uniprot.org/citations/33637374http://purl.uniprot.org/core/volume"27"xsd:string
http://purl.uniprot.org/citations/33637374http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33637374
http://purl.uniprot.org/citations/33637374http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33637374
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http://purl.uniprot.org/uniprot/#_Q16089-mappedCitation-33637374http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33637374
http://purl.uniprot.org/uniprot/#_P05230-mappedCitation-33637374http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33637374
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