Open Access

The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro

  • Authors:
    • Ying Zhou
    • Yuexin Sun
    • Wenjun Hou
    • Liwen Ma
    • Yue Tao
    • Dan Li
    • Cui Xu
    • Jun Bao
    • Weixin Fan
  • View Affiliations

  • Published online on: April 29, 2020     https://doi.org/10.3892/ijmm.2020.4592
  • Pages: 191-200
  • Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

AG490 is a selective inhibitor of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. The present study examined its effects on the abnormal behavior of human keloid fibroblasts (HKFs) and evaluated its potential use in the treatment of keloids. Human normal fibroblasts (HNFs) and HKFs were treated with increasing concentrations of AG490. The proliferation of HNFs and HKFs was inhibited by AG490 in both a time‑ and concentration‑dependent manner by increasing apoptosis and inducing G1 cell cycle arrest. The downregulation of cyclin D1 and connective tissue growth factor (CTGF) expression was associated with a decrease in STAT3 expression in response to AG490. The effects of AG490 on TGF‑β‑stimulated fibroblasts, including HNFs, HKFs and hypertrophic scar fibroblasts (HSFs) were also evaluated. The TGF‑β1‑stimulated excessive proliferation and CTGF production were markedly inhibited by the application of AG490 in the HNFs, HSFs and HKFs. In addition, the STAT3‑specific decoy oligodeoxynucleotides (SODNs) were transfected into HKFs. The invasive ability of the SODN‑transfected HKFs was determined and the expression of extracellular matrix components was quantified. Similarly, SODNs blocked the constitutive activation of STAT3. SODNs inhibited the invasion and progression of HKFs, possibly via the upregulation of the expression of tissue inhibitor of metalloproteinase‑2 (TIMP‑2), and the downregulation of the expression of matrix metalloproteinase‑2 (MMP‑2) and vascular endothelial growth factor (VEGF). On the whole, the findings of the present study demonstrate that STAT3‑specific elimination, such as the application of AG490 and decoy ODNs, may serve as promising therapeutic strategies for the treatment of keloids.
View Figures
View References

Related Articles

Journal Cover

July 2020
Volume 46 Issue 1

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Zhou, Y., Sun, Y., Hou, W., Ma, L., Tao, Y., Li, D. ... Fan, W. (2020). The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro. International Journal of Molecular Medicine, 46, 191-200. https://doi.org/10.3892/ijmm.2020.4592
MLA
Zhou, Y., Sun, Y., Hou, W., Ma, L., Tao, Y., Li, D., Xu, C., Bao, J., Fan, W."The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro". International Journal of Molecular Medicine 46.1 (2020): 191-200.
Chicago
Zhou, Y., Sun, Y., Hou, W., Ma, L., Tao, Y., Li, D., Xu, C., Bao, J., Fan, W."The JAK2/STAT3 pathway inhibitor, AG490, suppresses the abnormal behavior of keloid fibroblasts in vitro". International Journal of Molecular Medicine 46, no. 1 (2020): 191-200. https://doi.org/10.3892/ijmm.2020.4592