局部中长PDRN通过PI3K-Akt/TGF-β调节途径增强光损伤皮肤的皮肤细胞外基质修复
Topical medium-length PDRN enhances dermal extracellular matrix repair in photodamaged skin via PI3K-Akt/TGF-β-regulated pathways.
摘要(中文译文)
慢性紫外线（UV）暴露会破坏真皮成纤维细胞功能和细胞外基质（ECM）稳态，驱动光老化皮肤的结构特征。聚脱氧核糖核苷酸（PDRN）在注射应用中已显示出再生效应，但局部外用PDRN的作用机制和递送方式仍未被充分阐明。本研究探讨了一种中等长度PDRN制剂（PDRN-850K）在光损伤皮肤中的作用机制、皮肤递送及疗效。采用蛋白质印迹、基因表达分析和药理学抑制方法，在基础人真皮成纤维细胞中检测通路激活情况。通过重建表皮模型中的共聚焦拉曼光谱以及补充的离体和在体渗透研究评估皮肤递送。在UV照射的人离体皮肤模型中评估组织水平效应。通过一项为期28天、比较0.1% PDRN-850K眼霜与0.1%视黄醇的随机、双盲、半脸临床研究评估临床疗效。PDRN-850K激活了基础成纤维细胞中的PI3K-Akt、TGF-β/Smad及自噬相关信号通路，抑制这些通路可减弱ECM基因诱导。拉曼分析显示PDRN相关信号随时间依赖性分布至活性表皮区域，FITC标记猪皮肤及在体人拉曼预试验研究提供了进一步支持。在UV照射的离体皮肤中，PDRN-850K增加了活性表皮厚度，并上调了多种胶原、弹性纤维相关蛋白及YAP。临床上，与视黄醇相比，PDRN-850K在眼周皱纹、真皮厚度、密度及眼袋参数方面取得约两倍的改善，且耐受性良好。这些发现支持PDRN-850K作为一种针对光损伤皮肤的局部促修复方法。
Abstract
Chronic ultraviolet (UV) exposure disrupts dermal fibroblast function and extracellular matrix (ECM) homeostasis, driving the structural features of photoaged skin. Polydeoxyribonucleotide (PDRN) has shown regenerative effects in injectable applications, but the mechanism and delivery of topical PDRN remain insufficiently defined. This study investigated the mechanism, skin delivery, and efficacy of a medium-length PDRN preparation (PDRN-850K) in photodamaged skin. Pathway activation was examined in basal human dermal fibroblasts using western blotting, gene expression analysis, and pharmacological inhibition. Skin delivery was assessed by confocal Raman spectroscopy in a reconstructed epidermal model and by complementary ex vivo and in vivo penetration studies. Tissue-level effects were assessed in a UV-irradiated human ex vivo skin model. Clinical efficacy was evaluated in a randomized, double-blind, split-face study comparing 0.1% PDRN-850K eye cream with 0.1% retinol over 28 days. PDRN-850K activated PI3K-Akt, TGF-β/Smad, and autophagy-related signaling in basal fibroblasts, and inhibition of these pathways reduced ECM gene induction. Raman analysis demonstrated time-dependent distribution of PDRN-associated signal into viable epidermal regions, with additional support from FITC-labeled porcine skin and pilot in vivo human Raman studies. In UV-irradiated ex vivo skin, PDRN-850K increased viable epidermal thickness and upregulated multiple collagens, elastic fiber-associated proteins, and YAP. Clinically, PDRN-850K achieved approximately two-fold greater improvements in periocular wrinkles, dermal thickness, density, and eye bag parameters compared with retinol, with good tolerability. These findings support PDRN-850K as a topical pro-repair approach for photodamaged skin.
如何引用
AMA
Rui Ye, Qianqian Wang, Le Du, Li Li, Fan Hu. Topical medium-length PDRN enhances dermal extracellular matrix repair in photodamaged skin via PI3K-Akt/TGF-β-regulated pathways.. PloS one. 2026; doi:10.1371/journal.pone.0350905.
APA
Rui Ye, Qianqian Wang, Le Du, Li Li, Fan Hu (2026). Topical medium-length PDRN enhances dermal extracellular matrix repair in photodamaged skin via PI3K-Akt/TGF-β-regulated pathways.. PloS one. https://doi.org/10.1371/journal.pone.0350905
GB/T 7714
Rui Ye, Qianqian Wang, Le Du, Li Li, Fan Hu. Topical medium-length PDRN enhances dermal extracellular matrix repair in photodamaged skin via PI3K-Akt/TGF-β-regulated pathways.[J]. PloS one, 2026 doi:10.1371/journal.pone.0350905.
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