Open Access

Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart

  • Authors:
    • Fei Liu
    • Yuan Wen
    • Jinyuan Kang
    • Chunying Wei
    • Menghong Wang
    • Zeqi Zheng
    • Jingtian Peng
  • View Affiliations

  • Published online on: May 25, 2018     https://doi.org/10.3892/ijmm.2018.3707
  • Pages: 1436-1444
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The mechanism underlying the anti‑inflammatory or antifibrotic activity of erythropoietin (EPO) in myocardial fibrosis (MF) remains elusive. In the current study, abdominal aortic constriction (AAC) was performed on rats and EPO and/or Toll‑like receptor (TLR)4 were overexpressed in rat hearts through intramyocardial administration of lentivirus expressing the EPO and TLR4 genes. Hematoxylin and eosin staining and Masson's trichrome staining were performed on tissue sections from rat hearts for histopathological examination. ELISA was used to determine the levels of inflammatory mediators in serum. Gene expression levels were determined by quantitative polymerase chain reaction analysis and protein expression levels were determined by western blot analysis and immunofluorescence staining. The results indicated that EPO overexpression improved MF in rat hearts, by inhibiting the release of transforming growth factor (TGF)‑β1, tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β, IL‑17A, matrix metalloproteinase (MMP)‑9 and MMP‑2. Moreover, EPO overexpression suppressed the expression of TLR4, while promoting phosphoinositide 3‑kinase (PI3K) and phosphorylated AKT serine/threonine kinase 1 (Akt) expression levels. However, the beneficial effects of EPO were attenuated by overexpression of TLR4. In addition, inhibition of PI3K/Akt signaling activity by treatment with LY294002 markedly reversed the protective effect of EPO on the AAC‑induced MF. Taken together, the present study demonstrated that EPO may have a critical role against MF by activating PI3K/Akt signaling and by downregulating TLR4 expression, thereby inhibiting the release of TGF‑β1, TNF‑α, IL‑6, IL‑1β, IL‑17A, MMP‑9 and MMP‑2. These findings suggest that the PI3K/Akt/TLR4 signaling pathway is associated with the anti‑inflammatory effects of EPO and may play a role in attenuating AAC‑induced MF.
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September-2018
Volume 42 Issue 3

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

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Spandidos Publications style
Liu F, Wen Y, Kang J, Wei C, Wang M, Zheng Z and Peng J: Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart. Int J Mol Med 42: 1436-1444, 2018
APA
Liu, F., Wen, Y., Kang, J., Wei, C., Wang, M., Zheng, Z., & Peng, J. (2018). Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart. International Journal of Molecular Medicine, 42, 1436-1444. https://doi.org/10.3892/ijmm.2018.3707
MLA
Liu, F., Wen, Y., Kang, J., Wei, C., Wang, M., Zheng, Z., Peng, J."Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart". International Journal of Molecular Medicine 42.3 (2018): 1436-1444.
Chicago
Liu, F., Wen, Y., Kang, J., Wei, C., Wang, M., Zheng, Z., Peng, J."Regulation of TLR4 expression mediates the attenuating effect of erythropoietin on inflammation and myocardial fibrosis in rat heart". International Journal of Molecular Medicine 42, no. 3 (2018): 1436-1444. https://doi.org/10.3892/ijmm.2018.3707