关键词: Diabetic wound healing FGFR pathway Hippo pathway Nanocomposite

来  源:   DOI:10.1016/j.mtbio.2024.101104   PDF(Pubmed)

Abstract:
Clinical treatment of diabetic refractory ulcers is impeded by chronic inflammation and cell dysfunction associated with wound healing. The significant clinical application of bFGF in wound healing is limited by its instability in vivo. Sulfur has been applied for the treatment of skin diseases in the clinic for antibiosis. We previously found that sulfur incorporation improves the ability of selenium nanoparticles to accelerate wound healing, yet the toxicity of selenium still poses a risk for its clinical application. To obtain materials with high pro-regeneration activity and low toxicity, we explored the mechanism by which selenium-sulfur nanoparticles aid in wound healing via RNA-Seq and designed a nanoparticle called Nano-S@bFGF, which was constructed from sulfur and bFGF. As expected, Nano-S@bFGF not only regenerated zebrafish tail fins and promoted skin wound healing but also promoted skin repair in diabetic mice with a profitable safety profile. Mechanistically, Nano-S@bFGF successfully coactivated the FGFR and Hippo signalling pathways to regulate wound healing. Briefly, the Nano-S@bFGF reported here provides an efficient and feasible method for the synthesis of bioactive nanosulfur and bFGF. In the long term, our results reinvigorated efforts to discover more peculiar unique biofunctions of sulfur and bFGF in a great variety of human diseases.
摘要:
糖尿病难治性溃疡的临床治疗受到与伤口愈合相关的慢性炎症和细胞功能障碍的阻碍。bFGF在伤口愈合中的重要临床应用受到其体内不稳定性的限制。硫磺已在临床上用于皮肤疾病的治疗。我们以前发现硫的掺入提高了硒纳米颗粒加速伤口愈合的能力,然而,硒的毒性仍然对其临床应用构成风险。为了获得具有高促再生活性和低毒性的材料,我们探索了硒硫纳米颗粒通过RNA-Seq帮助伤口愈合的机制,并设计了一种名为Nano-S@bFGF的纳米颗粒,它由硫和bFGF构成。不出所料,Nano-S@bFGF不仅再生斑马鱼尾鳍并促进皮肤伤口愈合,而且还促进糖尿病小鼠的皮肤修复,具有有益的安全性。机械上,Nano-S@bFGF成功共激活FGFR和Hippo信号通路以调节伤口愈合。简而言之,本文报道的Nano-S@bFGF为合成生物活性纳米硫和bFGF提供了一种有效可行的方法。从长远来看,我们的结果重振了努力,以发现硫和bFGF在各种人类疾病中更独特的生物功能。
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