Open Access

Hepatocyte growth factor inhibits hypoxia/reoxygenation-induced activation of xanthine oxidase in endothelial cells through the JAK2 signaling pathway

  • Authors:
    • Ying Qian Zhang
    • Shun Ying Hu
    • Yun Dai Chen
    • Ming Zhou Guo
    • Shan Wang
  • View Affiliations

  • Published online on: August 18, 2016     https://doi.org/10.3892/ijmm.2016.2708
  • Pages: 1055-1062
  • Copyright: © Zhang 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

Vascular endothelial cells (ECs) appear to be one of the primary targets of hypoxia/reoxygenation (H/R) injury. In our previous study, we demonstrated that hepatocyte growth factor (HGF) exhibited a protective effect in cardiac microvascular endothelial cells (CMECs) subjected to H/R by inhibiting xanthine oxidase (XO) by reducing the cytosolic Ca2+ concentration increased in response to H/R. The precise mechanisms through which HGF inhibits XO activation remain to be determined. In the present study, we examined the signaling pathway through which HGF regulates Ca2+ concentrations and the activation of XO during H/R in primary cultured rat CMECs. CMECs were exposed to 4 h of hypoxia and 1 h of reoxygenation. The protein expression of XO and the activation of the phosphoinositide 3-kinase (PI3K), janus kinase 2 (JAK2) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways were detected by western blot analysis. Cytosolic calcium (Ca2+) concentrations and reactive oxygen species (ROS) levels were measured by flow cytometry. The small interfering RNA (siRNA)‑mediated knockdown of XO inhibited the increase in ROS production induced by H/R. LY294002 and AG490 inhibited the H/R-induced increase in the production and activation of XO. The PI3K and JAK2 signaling pathways were activated by H/R. The siRNA‑mediated knockdown of PI3K and JAK2 also inhibited the increase in the production of XO protein. HGF inhibited JAK2 activation whereas it had no effect on PI3K activation. The siRNA-mediated knockdown of JAK2 prevented the increase in cytosolic Ca2+ induced by H/R. Taken together, these findings suggest that H/R induces the production and activation of XO through the JAK2 and PI3K signaling pathways. Furthermore, HGF prevents XO activation following H/R primarily by inhibiting the JAK2 signaling pathway and in turn, inhibiting the increase in cytosolic Ca2+.
View Figures
View References

Related Articles

Journal Cover

October-2016
Volume 38 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang YQ, Hu SY, Chen YD, Guo MZ and Wang S: Hepatocyte growth factor inhibits hypoxia/reoxygenation-induced activation of xanthine oxidase in endothelial cells through the JAK2 signaling pathway. Int J Mol Med 38: 1055-1062, 2016.
APA
Zhang, Y.Q., Hu, S.Y., Chen, Y.D., Guo, M.Z., & Wang, S. (2016). Hepatocyte growth factor inhibits hypoxia/reoxygenation-induced activation of xanthine oxidase in endothelial cells through the JAK2 signaling pathway. International Journal of Molecular Medicine, 38, 1055-1062. https://doi.org/10.3892/ijmm.2016.2708
MLA
Zhang, Y. Q., Hu, S. Y., Chen, Y. D., Guo, M. Z., Wang, S."Hepatocyte growth factor inhibits hypoxia/reoxygenation-induced activation of xanthine oxidase in endothelial cells through the JAK2 signaling pathway". International Journal of Molecular Medicine 38.4 (2016): 1055-1062.
Chicago
Zhang, Y. Q., Hu, S. Y., Chen, Y. D., Guo, M. Z., Wang, S."Hepatocyte growth factor inhibits hypoxia/reoxygenation-induced activation of xanthine oxidase in endothelial cells through the JAK2 signaling pathway". International Journal of Molecular Medicine 38, no. 4 (2016): 1055-1062. https://doi.org/10.3892/ijmm.2016.2708