Li Lu, Liu Yuan, Chang Ruxue, Ye Tao, Li Ziyi, Huang Rufei, Wang Zhaoyang, Deng Jingxian, Xia Huan, Yang Yan, Huang Yadong
Department of Cell Biology, Jinan University, Guangzhou 510632, China.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China.
Antioxidants (Basel). 2024 Aug 19;13(8):1002. doi: 10.3390/antiox13081002.
The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage.
表皮屏障对于保护皮肤免受环境应激源和紫外线(UV)辐射至关重要。丝聚合蛋白-2(FLG2)是角质层中的一种关键蛋白质,在维持皮肤屏障稳态方面发挥着重要作用。然而,FLG2在减轻紫外线诱导的屏障破坏和光老化的不利影响方面的确切作用仍知之甚少。在本研究中,我们发现紫外线B(UVB)照射导致HaCaT角质形成细胞中FLG2表达降低,这与屏障功能受损相关。重组丝聚合蛋白-2(rFLG2)的施用增强了角质形成细胞分化,加强了屏障完整性,并提供了针对UVB照射诱导的细胞凋亡和氧化应激的保护作用。此外,在紫外线诱导的光损伤小鼠模型中,真皮注射rFLG2促进了表皮屏障的增强恢复,降低了氧化应激和炎症,并减轻了光老化典型的胶原蛋白降解。总体而言,我们的研究结果表明,靶向FLG2可能是预防和治疗皮肤屏障功能障碍以及对抗与光老化相关的衰老效应的一种策略性方法。rFLG2成为一种潜在可行的疗法,用于维持皮肤健康并预防因光损伤而加剧的皮肤衰老过程。