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Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice

  • Authors:
    • Tao Wang
    • Mengzhou Wang
    • Wuming Liu
    • Lin Zhang
    • Jia Zhang
    • Junzhou Zhao
    • Zheng Wu
    • Yi Lyu
    • Rongqian Wu
  • View Affiliations / Copyright

    Affiliations: National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 42
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    Published online on: January 7, 2025
       https://doi.org/10.3892/ijmm.2025.5483
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Abstract

Cold‑inducible RNA‑binding protein (CIRP) is a cold shock protein implicated in the regulation of multiple biological processes depending on its cellular localization. However, to the best of our knowledge, the role of CIRP in liver regeneration and injury after hepatectomy has not been investigated. The present study was therefore designed to explore whether CIRP is involved in liver regeneration after hepatectomy and its specific role and underlying molecular mechanism. The overall involvement of CIRP in liver regeneration and injury after hepatectomy was evaluated in CIRP‑deficient mice. C23, an antagonist of extracellular CIRP, was used to assess the effect of extracellular CIRP on liver regeneration and injury after hepatectomy. CIRP overexpression and short hairpin RNA plasmids were transfected into HepG2 cells to study the effect of intracellular CIRP on cell proliferation. The effects of extracellular CIRP on cell proliferation and injury were determined via the use of recombinant CIRP protein to stimulate HepG2 cells in vitro. The results indicated that both hepatic and serum CIRP levels significantly increased after partial hepatectomy. Additionally, CIRP deficiency impaired liver regeneration but alleviated liver injury after partial hepatectomy in mice. C23 administration attenuated liver injury and suppressed endoplasmic reticulum (ER) stress and oxidative stress. Loss‑ and gain‑of‑function analyses in HepG2 cells indicated that an increase in intracellular CIRP promoted cell proliferation via signal transducers and activation of transcription 3 (STAT3) signaling pathway activation. Moreover, recombinant CIRP had no effect on cell proliferation or STAT3 phosphorylation but induced ER stress, which was blocked by TAK242, an inhibitor of Toll‑like receptor 4 (TLR4), in HepG2 cells. Taken together, the results of the present study demonstrated that intracellular CIRP promotes liver regeneration by activating the STAT3 pathway, whereas extracellular CIRP induces ER stress possibly via the TLR4 signaling pathway after hepatectomy.
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Copy and paste a formatted citation
Spandidos Publications style
Wang T, Wang M, Liu W, Zhang L, Zhang J, Zhao J, Wu Z, Lyu Y and Wu R: Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice. Int J Mol Med 55: 42, 2025.
APA
Wang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Zhao, J. ... Wu, R. (2025). Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice. International Journal of Molecular Medicine, 55, 42. https://doi.org/10.3892/ijmm.2025.5483
MLA
Wang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Zhao, J., Wu, Z., Lyu, Y., Wu, R."Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice". International Journal of Molecular Medicine 55.3 (2025): 42.
Chicago
Wang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Zhao, J., Wu, Z., Lyu, Y., Wu, R."Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice". International Journal of Molecular Medicine 55, no. 3 (2025): 42. https://doi.org/10.3892/ijmm.2025.5483
Copy and paste a formatted citation
x
Spandidos Publications style
Wang T, Wang M, Liu W, Zhang L, Zhang J, Zhao J, Wu Z, Lyu Y and Wu R: Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice. Int J Mol Med 55: 42, 2025.
APA
Wang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Zhao, J. ... Wu, R. (2025). Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice. International Journal of Molecular Medicine, 55, 42. https://doi.org/10.3892/ijmm.2025.5483
MLA
Wang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Zhao, J., Wu, Z., Lyu, Y., Wu, R."Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice". International Journal of Molecular Medicine 55.3 (2025): 42.
Chicago
Wang, T., Wang, M., Liu, W., Zhang, L., Zhang, J., Zhao, J., Wu, Z., Lyu, Y., Wu, R."Intracellular CIRP promotes liver regeneration via STAT3 signaling pathway activation after partial hepatectomy in mice". International Journal of Molecular Medicine 55, no. 3 (2025): 42. https://doi.org/10.3892/ijmm.2025.5483
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