Aminoacyl-tRNA synthetase interacting multi-functional protein 1 attenuates liver fibrosis by inhibiting TGFβ signaling

  • Authors:
    • Jongchan Ahn
    • Mi Kwon Son
    • Kyung Hee Jung
    • Kwangil Kim
    • Gi Jin Kim
    • Soo-Hong Lee
    • Soon-Sun Hong
    • Sang Gyu Park
  • View Affiliations

  • Published online on: December 18, 2015     https://doi.org/10.3892/ijo.2015.3303
  • Pages: 747-755
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Abstract

The aminoacyl-tRNA synthetase interacting multi-functional protein 1 (AIMP1) participates in a variety of cellular processes, including translation, cell proliferation, inflammation and wound healing. Previously, we showed that the N-terminal peptide of AIMP1 (6-46 aa) induced ERK phosphorylation. Liver fibrosis is characterized by excessive deposition of extracellular matrix, which is induced by TGFβ signaling, and activated ERK is known to induce the phosphorylation of SMAD, thereby inhibiting TGFβ signaling. We assessed whether the AIMP1 peptide can inhibit collagen synthesis in hepatic stellate cells (HSCs) by activating ERK. The AIMP1 peptide induced phosphorylation of SMAD2 via ERK activation, and inhibited the nuclear translocation of SMAD, resulting in a reduction of the synthesis of type I collagen. The AIMP1 peptide attenuated liver fibrosis induced by CCl4, in a dose-dependent manner. Masson-Trichrome staining showed that the AIMP1 peptide reduced collagen deposition. Immunohistochemical staining showed that the levels of α-SMA, TGFβ and type I collagen were all reduced by the AIMP1 peptide. Liver toxicity analysis showed that the AIMP1 peptide improved the levels of relevant biological parameters in the blood. These results suggest that AIMP1 peptide may have potential for development as a therapeutic agent to treat liver fibrosis.
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February 2016
Volume 48 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Ahn, J., Son, M.K., Jung, K.H., Kim, K., Kim, G.J., Lee, S. ... Park, S.G. (2016). Aminoacyl-tRNA synthetase interacting multi-functional protein 1 attenuates liver fibrosis by inhibiting TGFβ signaling. International Journal of Oncology, 48, 747-755. https://doi.org/10.3892/ijo.2015.3303
MLA
Ahn, J., Son, M. K., Jung, K. H., Kim, K., Kim, G. J., Lee, S., Hong, S., Park, S. G."Aminoacyl-tRNA synthetase interacting multi-functional protein 1 attenuates liver fibrosis by inhibiting TGFβ signaling". International Journal of Oncology 48.2 (2016): 747-755.
Chicago
Ahn, J., Son, M. K., Jung, K. H., Kim, K., Kim, G. J., Lee, S., Hong, S., Park, S. G."Aminoacyl-tRNA synthetase interacting multi-functional protein 1 attenuates liver fibrosis by inhibiting TGFβ signaling". International Journal of Oncology 48, no. 2 (2016): 747-755. https://doi.org/10.3892/ijo.2015.3303