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TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway

  • Authors:
    • Yan-Lin Cao
    • Yang Duan
    • Li-Xin Zhu
    • Ye-Nan Zhan
    • Shao-Xiong Min
    • An-Min Jin
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China
    Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 391-398
    |
    Published online on: June 8, 2016
       https://doi.org/10.3892/ijmm.2016.2631
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Abstract

Hypertrophy of the ligamentum flavum (LF) is one of the key pathomechanisms of lumbar spinal stenosis (LSS). Transforming growth factor (TGF)-β1 is abundantly expressed in hypertrophied degenerative LF tissues from LSS. However, the molecular mechanisms underling the association between TGF-β1 and LF hypertrophy have not yet been fully elucidated. In this study, we investigated the important role of the mitogen-activated protein kinase (MAPK) pathway in the pathogenesis of LSS by analyzing the expression of connective tissue growth factor (CTGF) and extracellular matrix (ECM) components (collagen I and collagen III) in TGF-β1-treated LF cells. Cell growth assay revealed that TGF-β1, in association with CTGF, enhanced the the proliferation of LF cells, and we found that TGF-β1 also elevated CTGF expression and subsequently enhanced the mRNA expression of collagen I and collagen III. The increased mRNA expression levels of CTGF, collagen I and collagen III were abolished by p38 inhibitors. Both immunofluorescence imaging and western blot analysis of p38 and p-p38 revealed the increased expression and phosphorylation of p38. Silencing the expression of p38 by siRNA in LF cells decreased the protein expression of p38, p-p38 and CTGF, as well as the mRNA expression of CTGF, collagen I and collagen III. Taken together, our findings indicate that TGF-β1, in association with the increased expression of CTGF, contribute to the homeostasis of the ECM and to the hypertrophy of LF through the p38 MAPK pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Cao Y, Duan Y, Zhu L, Zhan Y, Min S and Jin A: TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway. Int J Mol Med 38: 391-398, 2016.
APA
Cao, Y., Duan, Y., Zhu, L., Zhan, Y., Min, S., & Jin, A. (2016). TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway. International Journal of Molecular Medicine, 38, 391-398. https://doi.org/10.3892/ijmm.2016.2631
MLA
Cao, Y., Duan, Y., Zhu, L., Zhan, Y., Min, S., Jin, A."TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway". International Journal of Molecular Medicine 38.2 (2016): 391-398.
Chicago
Cao, Y., Duan, Y., Zhu, L., Zhan, Y., Min, S., Jin, A."TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway". International Journal of Molecular Medicine 38, no. 2 (2016): 391-398. https://doi.org/10.3892/ijmm.2016.2631
Copy and paste a formatted citation
x
Spandidos Publications style
Cao Y, Duan Y, Zhu L, Zhan Y, Min S and Jin A: TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway. Int J Mol Med 38: 391-398, 2016.
APA
Cao, Y., Duan, Y., Zhu, L., Zhan, Y., Min, S., & Jin, A. (2016). TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway. International Journal of Molecular Medicine, 38, 391-398. https://doi.org/10.3892/ijmm.2016.2631
MLA
Cao, Y., Duan, Y., Zhu, L., Zhan, Y., Min, S., Jin, A."TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway". International Journal of Molecular Medicine 38.2 (2016): 391-398.
Chicago
Cao, Y., Duan, Y., Zhu, L., Zhan, Y., Min, S., Jin, A."TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway". International Journal of Molecular Medicine 38, no. 2 (2016): 391-398. https://doi.org/10.3892/ijmm.2016.2631
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