《药物化学杂志》

https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c01734

Cyclic Heptapeptide FZ1 Acts as an Integrin αvβ3 Agonist to Facilitate Diabetic Skin Wound Healing by Enhancing Angiogenesis

摘要

Diabetic wound healing remains a persistent clinical challenge, necessitating the development of effective therapeutic agents and a deeper understanding of regulatory mechanisms. The cyclic heptapeptide FZ1, characterized by favorable biocompatibility, exhibited significantly greater efficacy than rh-bFGF and CyRL-QN15 in promoting cell proliferation and migration. In diabetic wound models, FZ1 markedly accelerated tissue regeneration and stimulated angiogenesis, as indicated by the upregulation of CD31 and α-SMA. Mechanistic investigations combining single-cell RNA sequencing, RNA interference, surface plasmon resonance, and molecular docking revealed that FZ1 directly bound to integrin αvβ3, activating FAK-dependent AKT and ERK1/2 signaling pathways to induce VEGFC expression. This signaling cascade enhanced endothelial cell proliferation, migration, and tube formation, collectively contributing to improved angiogenesis and wound closure. These findings identify FZ1 as the first peptide agonist targeting integrin αvβ3 with demonstrated pro-healing effects in diabetic wounds, representing a promising therapeutic candidate supported by defined molecular mechanisms.

该研究的实验部分，肽类化合物（B1−1、B2−1、E1−1、E2−1、N2−1、G1−1、J1−1、B1−P1、B2−P1、E1-P1、E1-P2、N−P1、RL-QN15、CyOM‑LV20、CyRL‑QN15及FZ1；纯度>95%）由武汉天德生物科技有限公司（中国武汉）合成。（Peptide Synthesis. Peptides (B1−1, B2−1, E1−1, E2−1, N2−1, G1−1, J1−1, B1−P1, B2−P1, E1-P1, E1-P2, N−P1, RL-QN15, CyOM‑LV20, CyRL‑QN15, and FZ1; purity >95%) were synthesized by Wuhan Tanda Biotechnology Co., Ltd. (Wuhan, China). The de novo structure of FZ1 was predicted using the PEP-FOLD3 online platform.）