Zhu Jiawen, Zhong Xinhua, Liao Hui, Cong Jianhang, Wu Qiqi, Liang Shuang, Xiang Qi
State Key Laboratory of Bioactive Molecules and Drug Gability Assessment, Jinan University, Guangzhou 510632, China.
Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, China.
Bioengineering (Basel). 2024 Apr 26;11(5):426. doi: 10.3390/bioengineering11050426.
Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is marked by impaired skin barrier function and persistent pruritus. It significantly deteriorates patients' quality of life, making it one of the most burdensome non-lethal skin disorders. Filaggrin plays a crucial role in the pathophysiology of barrier disruption in AD, interacting with inflammatory mediators. It is an integral part of the extracellular matrix architecture, serving to protect the skin barrier and attenuate the inflammatory cascade. In this study, we engineered a novel recombinant human filaggrin (rhFLA-10) expression vector, which was subsequently synthesized and purified. In vitro and ex vivo efficacy experiments were conducted for AD. rhFLA-10, at low concentrations (5 to 20 μg/mL), was non-toxic to HACaT cells, significantly inhibited the degranulation of P815 mast cells, and was readily absorbed by cells, thereby exerting a soothing therapeutic effect. Furthermore, rhFLA-10 demonstrated anti-inflammatory properties ( < 0.05). In vivo, efficacy experiments further substantiated that rhFLA-10 could effectively ameliorate AD in mice and facilitate the repair of damaged skin ( < 0.001). These findings underscore the considerable potential of rhFLA-10 in the treatment of AD.
特应性皮炎（AD）是一种常见的慢性炎症性皮肤病，其特征为皮肤屏障功能受损和持续性瘙痒。它显著降低患者的生活质量，使其成为最具负担的非致命性皮肤病之一。丝聚合蛋白在AD的屏障破坏病理生理学中起着关键作用，与炎症介质相互作用。它是细胞外基质结构的一个组成部分，用于保护皮肤屏障并减弱炎症级联反应。在本研究中，我们构建了一种新型重组人丝聚合蛋白（rhFLA-10）表达载体，随后进行了合成和纯化。针对AD进行了体外和离体疗效实验。低浓度（5至20μg/mL）的rhFLA-10对HACaT细胞无毒，显著抑制P815肥大细胞的脱颗粒，并且易于被细胞吸收，从而发挥舒缓的治疗作用。此外，rhFLA-10表现出抗炎特性（<0.05）。在体内，疗效实验进一步证实rhFLA-10可有效改善小鼠的AD并促进受损皮肤的修复（<0.001）。这些发现强调了rhFLA-10在治疗AD方面的巨大潜力。
