Open Access

CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis

  • Authors:
    • Honghai Xu
    • Cong Liu
    • Zhengming Sun
    • Xiong Guo
    • Yuelin Zhang
    • Mengting Liu
    • Peng Li
  • View Affiliations

  • Published online on: April 21, 2015     https://doi.org/10.3892/ijmm.2015.2190
  • Pages: 123-129
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Epidural fibrosis is characterized by the development of dense and thick scar tissue adjacent to the dural mater and ranked as the major contributor for post-operative pain recurrence after laminectomy or discectomy. Recently, CCN5 exhibited an inhibitory effect on connective tissue growth factor (CTGF)/CCN2 (a critical regulator for fibrotic disease)‑mediated fibrogenesis. However, its function in epidural fibrosis and the underlying mechanisms involved remain to be determined. In this study, an obvious downregulation of CCN5 was observed in scar tissues from laminectomized rats, concomitant with a marked upregulation of CCN2, suggesting a potential negative regulatory role of CCN5 in fibrogenesis. Furthermore, CCN5 overexpression notably mitigated transforming growth factor‑β1-enhanced fibroblast viability and proliferation. Of note, CCN5 upregulation inhibited the switch of fibroblasts into myofibroblasts as its overexpression abrogated the expression of the myofibroblast marker, α-smooth muscle actin (α-SMA). CCN5 upregulation also reduced an increase in collagen type I, α1 (COL1A1) and total collagen concentrations. Additionally, CCN5 over­expression decreased CCN2 expression and increased Smad6 phosphorylation. Mechanism analysis revealed that blocking Smad6 signaling significantly ameliorated the inhibitory effect of CCN5 on the CCN2 levels, accompanied by the reduction in cell proliferation and collagen production. These results confirm that CCN5 exerts an anti-fibrotic function by regulating the Smad6-CCN2 pathway, thereby indicating a potential approach for ameliorating epidural fibrosis after laminectomy.
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July-2015
Volume 36 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Xu H, Liu C, Sun Z, Guo X, Zhang Y, Liu M and Li P: CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis. Int J Mol Med 36: 123-129, 2015.
APA
Xu, H., Liu, C., Sun, Z., Guo, X., Zhang, Y., Liu, M., & Li, P. (2015). CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis. International Journal of Molecular Medicine, 36, 123-129. https://doi.org/10.3892/ijmm.2015.2190
MLA
Xu, H., Liu, C., Sun, Z., Guo, X., Zhang, Y., Liu, M., Li, P."CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis". International Journal of Molecular Medicine 36.1 (2015): 123-129.
Chicago
Xu, H., Liu, C., Sun, Z., Guo, X., Zhang, Y., Liu, M., Li, P."CCN5 attenuates profibrotic phenotypes of fibroblasts through the Smad6-CCN2 pathway: Potential role in epidural fibrosis". International Journal of Molecular Medicine 36, no. 1 (2015): 123-129. https://doi.org/10.3892/ijmm.2015.2190