Open Access

Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms

  • Authors:
    • Pengran Liu
    • Dan Zhang
    • Guixiong Huang
    • Mingdi Xue
    • Ying Fang
    • Lin Lu
    • Jiayao Zhang
    • Mao Xie
    • Zhewei Ye
  • View Affiliations

  • Published online on: November 16, 2022     https://doi.org/10.3892/ijmm.2022.5205
  • Article Number: 2
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Excessive proliferation and migration of fibroblasts in the lumbar laminectomy area can lead to epidural fibrosis, eventually resulting in failed back surgery syndrome. It has been reported that laminin α1, a significant biofunctional glycoprotein in the extracellular matrix, is involved in several fibrosis‑related diseases, such as pulmonary, liver and keloid fibrosis. However, the underlying mechanism of laminin α1 in epidural fibrosis remains unknown. The present study aimed to explore the effect and mechanism of laminin α1 in fibroblast proliferation, apoptosis and migration, and epidural fibrosis. Following the establishment of a laminectomy model, hematoxylin and eosin, Masson's trichrome and immunohistochemical staining were performed to determine the degree of epidural fibrosis, the number of fibroblasts, collagen content and the epidural expression levels of laminin α1, respectively. Furthermore, a stable small interfering RNA system was used to knock down the expression of laminin α1 in fibroblasts. The transfection efficiency was confirmed by reverse transcription‑quantitative PCR and immunofluorescence staining. Western blot analysis, scratch wound assay, EdU incorporation assay, flow cytometric analysis and Cell Counting Kit 8 assay were performed to assess the proliferation, apoptosis, migration and viability of fibroblasts, as well as the expression levels of the AKT/mechanistic target of rapamycin (mTOR) signaling‑related proteins. In vivo experiments revealed that laminin α1 was positively and time‑dependently associated with epidural fibrosis. In addition, laminin α1 knockdown attenuated cell proliferation, viability and migration, and promoted apoptosis. Furthermore, the results revealed that the activation of the AKT/mTOR signaling pathway was involved in the aforementioned processes. Overall, the current study illustrated the positive association between laminin α1 and epidural fibrosis, and also verified the effect of laminin α1 on fibroblast proliferation, apoptosis and migration. Furthermore, the results suggested that the AKT/mTOR signaling pathway may serve a significant role in regulating the behavior of laminin α1‑induced fibroblasts.
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January-2023
Volume 51 Issue 1

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

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Copy and paste a formatted citation
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Spandidos Publications style
Liu P, Zhang D, Huang G, Xue M, Fang Y, Lu L, Zhang J, Xie M and Ye Z: Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms. Int J Mol Med 51: 2, 2023
APA
Liu, P., Zhang, D., Huang, G., Xue, M., Fang, Y., Lu, L. ... Ye, Z. (2023). Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms. International Journal of Molecular Medicine, 51, 2. https://doi.org/10.3892/ijmm.2022.5205
MLA
Liu, P., Zhang, D., Huang, G., Xue, M., Fang, Y., Lu, L., Zhang, J., Xie, M., Ye, Z."Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms". International Journal of Molecular Medicine 51.1 (2023): 2.
Chicago
Liu, P., Zhang, D., Huang, G., Xue, M., Fang, Y., Lu, L., Zhang, J., Xie, M., Ye, Z."Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms". International Journal of Molecular Medicine 51, no. 1 (2023): 2. https://doi.org/10.3892/ijmm.2022.5205