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基于理论论证构建的 PDGF 衍生融合肽二聚体形式的功能表征。

Functional characterization of the dimeric form of PDGF-derived fusion peptide fabricated based on theoretical arguments.

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, PO BoX 14515-775, Tehran, Iran.

Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran.

出版信息

Sci Rep. 2024 Jan 10;14(1):1003. doi: 10.1038/s41598-024-51707-2.

Abstract

A skin wound leads to the loss of skin integrity and the influx of pathogens into the tissue. Platelet-derived growth factors (PDGFs) are cytokines released from alpha granules during wound healing and interact with their cell surface receptors and activate signals involved in chemotaxis, growth, proliferation, and differentiation pathways. Due to the low stability of growth factors (GFs), a new peptide-derived PDGF-BB was designed, expressed in the Shuffle strain of E. coli, and purified by Ni-NTA agarose affinity column chromatography. The effect of fusion peptide was then evaluated on L929 fibroblast cells and animal models with skin lesions. In vitro, studies showed that the peptide led to an increase in the migration of fibroblast cells in the scratch assay. Its positive effect on wound healing was also observed in the skin-injured rats after 3, 7, and 12 days. A significant rise in neutrophils and granular tissue formation, re-epithelialization, angiogenesis, and collagen formation was exhibited on the third day of treatment when compared to the control group. The results showed that, despite reducing PDGF size, the fusion peptide was able to maintain at least some of the known functions attributed to full-length PDGF and showed positive results in wound healing.

摘要

皮肤创伤会导致皮肤完整性丧失,并使病原体侵入组织。血小板衍生生长因子 (PDGFs) 是创伤愈合过程中从α颗粒中释放的细胞因子,与细胞表面受体相互作用并激活参与趋化、生长、增殖和分化途径的信号。由于生长因子 (GFs) 的稳定性低,因此设计了一种新的肽衍生 PDGF-BB,在大肠杆菌 Shuffle 菌株中表达,并通过 Ni-NTA 琼脂糖亲和柱层析进行纯化。然后评估融合肽对 L929 成纤维细胞和有皮肤损伤的动物模型的作用。在体外研究中,研究表明该肽可导致划痕试验中成纤维细胞的迁移增加。在皮肤损伤大鼠中,在第 3、7 和 12 天时也观察到对伤口愈合的积极影响。与对照组相比,在治疗的第 3 天,中性粒细胞和颗粒组织形成、再上皮化、血管生成和胶原蛋白形成明显增加。结果表明,尽管融合肽减小了 PDGF 的大小,但它能够维持至少部分已知的全长 PDGF 所具有的功能,并在伤口愈合中显示出积极的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c63/10781716/3e6cefc9aad3/41598_2024_51707_Fig1_HTML.jpg

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