Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200040, China; Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200030, China.
Department of Pain, Huadong Hospital, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200040, China; Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200030, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200030, China.
Cell Signal. 2022 Dec;100:110463. doi: 10.1016/j.cellsig.2022.110463. Epub 2022 Sep 6.
Treatment of skeletal muscle atrophy and strengthening the muscles remain a challenge in modern medicine. Studies have shown that photobiomodulation can inhibit skeletal muscle atrophy and aid in functional recovery. Near-infrared radiation (NIR) therapy has emerged as a complementary therapy for the treatment of skeletal muscle atrophy, but its underlying mechanism remains unclear. Polypyrrole (PPy) is an organic polymer with strong near-infrared absorption, which can generate heat from absorbed NIR. In this study, MHC immunofluorescence staining was performed on C2C12 myoblasts to investigate the differentiation of C2C12 cells after NIR-triggered PPy exposure. As TNF-α-induced C2C12 myotubes were used as a model of muscular atrophy. Giemsa staining was used to determine the myotube diameter. Western blot analysis was performed to examine the proteins involved in the differentiation and atrophy of muscle cells, as well as in the Akt/P70S6K signaling pathway. PPy triggered by NIR promoted the differentiation of C2C12 cells, inhibited C2C12 myotube atrophy caused by TNF-α, and downregulated the expression levels of Atrogin-1 and MuRF 1 protein. In addition, we determined that Akt/P70S6K signaling pathway activity plays a crucial role in the therapeutic effect of NIR-triggered polypyrrole, which was further confirmed by the administration of the Akt inhibitor GDC0068. The optimal conditions for these effects were a PPy concentration of 0.125 mg/ml and NIR exposure for 80 s. We show that the photothermal effect of PPy triggered by near-infrared light can increase the beneficial effects of NIR, promote the differentiation of C2C12 cells, and improve C2C12 myotube atrophy, laying a foundation for its future clinical use.
骨骼肌萎缩的治疗和肌肉增强仍然是现代医学的挑战。研究表明,光生物调节可以抑制骨骼肌萎缩并有助于功能恢复。近红外辐射(NIR)治疗已成为治疗骨骼肌萎缩的辅助治疗方法,但其潜在机制尚不清楚。聚吡咯(PPy)是一种具有强近红外吸收的有机聚合物,可从吸收的 NIR 中产生热量。在这项研究中,对 C2C12 成肌细胞进行 MHC 免疫荧光染色,以研究 NIR 触发 PPy 暴露后 C2C12 细胞的分化。由于 TNF-α诱导的 C2C12 肌管被用作肌肉萎缩模型。使用 Giemsa 染色来确定肌管直径。进行 Western blot 分析以检查参与肌肉细胞分化和萎缩以及 Akt/P70S6K 信号通路的蛋白质。NIR 触发的 PPy 促进了 C2C12 细胞的分化,抑制了 TNF-α引起的 C2C12 肌管萎缩,并下调了 Atrogin-1 和 MuRF 1 蛋白的表达水平。此外,我们确定 Akt/P70S6K 信号通路活性在 NIR 触发聚吡咯的治疗效果中起着至关重要的作用,这通过 Akt 抑制剂 GDC0068 的给药进一步得到证实。这些效果的最佳条件是 PPy 浓度为 0.125mg/ml 和 NIR 暴露 80s。我们表明,近红外光触发的 PPy 的光热效应可以增加 NIR 的有益效果,促进 C2C12 细胞的分化,并改善 C2C12 肌管萎缩,为其未来的临床应用奠定了基础。