Anti photoaging mechanism of a novel recombinant human fibronectin peptide (rhFNP) derived from the extracellular matrix

源自细胞外基质的新型重组人纤连蛋白肽(rhFNP)的抗光老化机制

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作者:Yuan Wang, Qirong Zhang, Hui Liao, Xiangyi Lu, Jianhang Cong, Zhao Liu, Qin Liu, Chaoqing Deng, Yong Cheng, Peng Shu, Qi Xiang

Abstract

Photoaging is a major cause of skin ageing. Ultraviolet radiation is a key factor in this process, as it can increase the expression of inflammatory factors, promote an inflammatory response, and disrupt the balance between extracellular matrix (ECM) synthesis and degradation, resulting in impaired skin barrier function and increased skin sensitivity. Therefore, anti-inflammation and ECM remodelling are important directions in skin anti-aging research. To simulate the ECM, we constructed a novel recombinant human fibronectin peptide (rhFNP) using synthetic biology. HaCaT, P815, and NHEK cells, Zebrafish, and a KM mouse photoaging model, along with transcriptomics analysis, were used to test rhFNP function and effects. rhFNP mediated HaCaT cell adhesion and migration (p < 0.05), inhibited MMPs gene expression and increased protein expression of Col1α1, Col3α1, and LOR in the NHEK photoaging model, and promoted gene expression of FLG and LOR in Zebrafish (p < 0.01). Moreover, rhFNP inhibited P815 degranulation induced by C48/80 (p < 0.001) and RAW264.7 secretion of TNF-α induced by Lipopolysaccharide (LPS) (p < 0.001). In the KM mouse photoaging model, rhFNP reduced skin damage, ameliorated redness in the sixth week, reduced abnormal thickening of the skin epidermis and dermis, and increased the skin collagen content (p < 0.01, vs. Modol). Transcriptomics analysis showed rhFNP may reduce IL-1α, IL-1β, and IL-18 through immune response, inhibit metalloproteinases, and promote ECM synthesis gene expression.

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