An Ultrashort Peptide-Based Supramolecular Hydrogel Mimicking IGF-1 to Alleviate Glucocorticoid-Induced Sarcopenia
Yuna Shang, Mingjie Kuang, Zhongyan Wang, Ying Huang, Lulu Liu, Xige Zhao, Rui Zhang, Yanhong Zhao, Rong Peng, Shenghuan Sun, Qiang Yang, Zhimou Yang
Abstract
Sarcopenia is a common disease in older people due to aging, and it can also occur in midlife because of diseases including cancer. Sarcopenia, characterized by rapid loss of muscle mass and accelerated loss of function, can lead to adverse outcomes such as frailty, falls, and even mortality. The development of pharmacological and therapeutic approaches to treat sarcopenia remains challenging. The growth status and quantity of myoblasts are the key factors directly affecting muscle formation. Therefore, enhancing the function of myoblasts is crucial for the treatment of sarcopenia. In our study, we introduced an insulin-like growth factor-I (IGF-1) mimicking supramolecular nanofibers/hydrogel formed by Nap-FFGSSSR that effectively promoted proliferation and significantly reduced dexamethasone-induced apoptosis of myoblasts, assisted myoblasts to differentiate into myotubes, and prevented the fibrosis of muscle tissue and the deposition of collagen, ultimately achieving outstanding effects in the treatment of sarcopenia. The RNA-sequencing results revealed that our nanofibers possessed similar bioactivity to the growth factor IGF-1, which increased the phosphorylation of Akt by activating the insulin signaling pathway. We prepared novel supramolecular nanomaterials to reverse glucocorticoid-induced myoblast dysfunction, which was promising for the treatment of muscular atrophy. In addition, we envisioned the generation of biofunctional nanomaterials by molecular self-assembly for the treatment of chronic diseases in middle-aged and older people.