Open Access

Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1

  • Authors:
    • Xiaoshu Pu
    • Xiaolei Cao
    • Hongyan Liu
    • Wenlian Huang
    • Lanfang Zhang
    • Ting Jiang
  • View Affiliations

  • Published online on: May 11, 2023     https://doi.org/10.3892/etm.2023.12009
  • Article Number: 310
  • Copyright: © Pu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Isorhamnetin (IH) is a type of flavonoid with multiple biological activities, including cardioprotective, antitumor, anti‑inflammatory and antioxidant activities. However, the role and potential mechanism of IH in keloids are still not completely understood. The aim of the present study was to explore how IH affects keloid progression. In the present study, cell proliferation was evaluated using the Cell Counting Kit‑8 assay and immunofluorescence. Wound healing and Transwell assays were performed to assess cell migration and invasion, respectively. The expression levels of fibrosis‑related proteins were measured using western blot analysis and immunofluorescence. In addition, the binding between IH and sphingosine‑1‑phosphate receptor‑1 (S1PR1) was analyzed using the TargetNet database, and molecular docking was performed using Zinc, PubChem, AutoDockTools 1.5.6 and Discovery Studio 4.5 software. The expression levels of proteins in the PI3K/AKT pathway were detected by western blot analysis. The results showed that IH inhibited the proliferation, invasion, migration and fibrosis of keloid fibroblasts. The binding of IH and S1PR1 was verified and molecular docking was performed. Notably, IH significantly suppressed the expression levels of S1PR1, phosphorylated (p)‑PI3K and p‑AKT. Furthermore, the silencing of S1PR1 suppressed the cell proliferation, migration, invasion and fibrosis of keloid fibroblasts, as well as the expression of the PI3K/AKT pathway proteins. Conversely, S1PR1 upregulation reversed the inhibitory effects of IH on keloid fibroblast proliferation, migration, invasion and fibrosis. In conclusion, the results revealed that IH suppressed the proliferation, migration, invasion and fibrosis of keloid fibroblasts by targeting the S1PR1/PI3K/AKT pathway, suggesting that IH may be a promising drug for the treatment of keloids.
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July-2023
Volume 26 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Pu X, Cao X, Liu H, Huang W, Zhang L and Jiang T: Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1. Exp Ther Med 26: 310, 2023
APA
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., & Jiang, T. (2023). Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1. Experimental and Therapeutic Medicine, 26, 310. https://doi.org/10.3892/etm.2023.12009
MLA
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., Jiang, T."Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1". Experimental and Therapeutic Medicine 26.1 (2023): 310.
Chicago
Pu, X., Cao, X., Liu, H., Huang, W., Zhang, L., Jiang, T."Isorhamnetin attenuates the proliferation, invasion, migration and fibrosis of keloid fibroblasts by targeting S1PR1". Experimental and Therapeutic Medicine 26, no. 1 (2023): 310. https://doi.org/10.3892/etm.2023.12009