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bioRxiv · 10.1101/2023.04.01.535227

Anti-nucleolin aptamer, iSN04, inhibits the inflammatory responses in myoblasts by modulating the β-catenin/NF-κB signaling pathway

Yamamoto, M.·Miyoshi, M.·Morioka, K.·Mitani, T.·Takaya, T.
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Abstract

A myogenetic oligodeoxynucleotide, iSN04, is the 18-base single-stranded DNA that acts as an anti-nucleolin aptamer. iSN04 has been reported to restore myogenic differentiation by suppressing inflammatory responses in myoblasts isolated from patients with diabetes or healthy myoblasts exposed to cancer-releasing factors. Thus, iSN04 is expected to be a nucleic acid drug for the muscle wasting associated with chronic diseases. The present study investigated the anti-inflammatory mechanism of iSN04 in the murine myoblast cell line C2C12. Tumor necrosis factor- (TNF-) or Toll-like receptor (TLR) ligands (Pam3CSK4 and FSL-1) induced nuclear translocation and transcriptional activity of nuclear factor-{kappa}B (NF-{kappa}B), resulting in upregulated expression of TNF- and interleukin-6. Pre-treatment with iSN04 significantly suppressed these inflammatory responses by inhibiting the nuclear accumulation of {beta}-catenin induced by TNF- or TLR ligands. These results demonstrate that antagonizing nucleolin with iSN04 downregulates the inflammatory effect mediated by the {beta}-catenin/NF-{kappa}B signaling pathway in myoblasts. In addition, the anti-inflammatory effects of iSN04 were also observed in smooth muscle cells and pre-adipocytes, suggesting that iSN04 may be useful in preventing inflammation induced by metabolic disorders.

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Yamamoto, M., Miyoshi, M., Morioka, K., Mitani, T., Takaya, T.. 2023-04-02. Anti-nucleolin aptamer, iSN04, inhibits the inflammatory responses in myoblasts by modulating the β-catenin/NF-κB signaling pathway. https://doi.org/10.1101/2023.04.01.535227

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