Induction of MMP‑1 and ‑3 by cyclical mechanical stretch is mediated by IL‑6 in cultured fibroblasts of keratoconus

  • Authors:
    • Gen‑Lai Du
    • Wei‑Yi Chen
    • Xiao‑Na Li
    • Rui He
    • Peng‑Fei Feng
  • View Affiliations

  • Published online on: April 4, 2017     https://doi.org/10.3892/mmr.2017.6433
  • Pages: 3885-3892
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In order to understand the effect of mechanical stretch on corneal extracellular matrix remodeling, human keratoconus fibroblasts (HKCFBs) were subjected to cyclic stretch in vitro and the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and inflammatory cytokines were evaluated. HKCFBs were seeded into a flexible membrane base and subjected to a cyclic stretch regimen of 10% equibiaxial stretch at a stretching frequency of 1 Hz for 6 h using a Flexcell tension unit. An antibody directed against interleukin‑6 (IL‑6 Ab) was used to investigate the roles of IL‑6 on mechanical stretch mediated regulation of MMP in HKCFBs. Culture supernatants were assayed using an enzyme‑linked immunosorbent assay for MMP‑1 and ‑3, TIMP‑1 and ‑2, and IL‑6. Total RNA from the cells was extracted, and quantitative polymerase chain reaction was used to determine mRNA for MMP‑1 and ‑3, TIMP‑1 and ‑2, and IL‑6. In stretched cells, levels of MMP‑1 and ‑3 demonstrated an increase compared with unstretched cells, but levels of TIMP‑1, and ‑2 revealed a decrease. Mechanical stretch significantly increased the mRNA expression and protein synthesis of IL‑6 compared with unstretched cells. IL‑6 induced MMP‑1 and ‑3 expression, whereas no significant effects were observed in levels of TIMP‑1 and ‑2 compared with the untreated control groups. Additionally, the IL‑6 Ab markedly inhibited the stretch‑induced increase in MMP‑1 and ‑3 in culture supernatants in a dose‑dependent manner. No significant differences in TIMP‑1 and ‑2 protein levels were detected between stretched cells treated with IL‑6 Ab and stretched cells without IL‑6 Ab treatment. These results indicate that cyclical mechanical stretch augments IL‑6 production and MMP expression, and reduces levels of TIMP in HKCFBs. Thus, it is suggested that IL‑6 mediates the stretch‑induced MMP expression.
View Figures
View References

Related Articles

Journal Cover

June-2017
Volume 15 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Du GL, Chen WY, Li XN, He R and Feng PF: Induction of MMP‑1 and ‑3 by cyclical mechanical stretch is mediated by IL‑6 in cultured fibroblasts of keratoconus. Mol Med Rep 15: 3885-3892, 2017
APA
Du, G., Chen, W., Li, X., He, R., & Feng, P. (2017). Induction of MMP‑1 and ‑3 by cyclical mechanical stretch is mediated by IL‑6 in cultured fibroblasts of keratoconus. Molecular Medicine Reports, 15, 3885-3892. https://doi.org/10.3892/mmr.2017.6433
MLA
Du, G., Chen, W., Li, X., He, R., Feng, P."Induction of MMP‑1 and ‑3 by cyclical mechanical stretch is mediated by IL‑6 in cultured fibroblasts of keratoconus". Molecular Medicine Reports 15.6 (2017): 3885-3892.
Chicago
Du, G., Chen, W., Li, X., He, R., Feng, P."Induction of MMP‑1 and ‑3 by cyclical mechanical stretch is mediated by IL‑6 in cultured fibroblasts of keratoconus". Molecular Medicine Reports 15, no. 6 (2017): 3885-3892. https://doi.org/10.3892/mmr.2017.6433