1. Academic Validation
  2. Recombinant filaggrin-2 improves skin barrier function and attenuates ultraviolet B (UVB) irradiation-induced epidermal barrier disruption

Recombinant filaggrin-2 improves skin barrier function and attenuates ultraviolet B (UVB) irradiation-induced epidermal barrier disruption

  • Int J Biol Macromol. 2024 Nov;281(Pt 1):136064. doi: 10.1016/j.ijbiomac.2024.136064.
Zhaoyang Wang 1 Hongxia Chen 1 Yuxin Wang 1 Chunna Wu 2 Tao Ye 2 Huan Xia 3 Rufei Huang 2 Jingxian Deng 2 Ziyi Li 2 Yadong Huang 4 Yan Yang 5
Affiliations

Affiliations

  • 1 Department of Cell Biology, Jinan University, Guangzhou 510632, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China.
  • 2 Department of Cell Biology, Jinan University, Guangzhou 510632, China.
  • 3 Jinan University&TYRAN Cosmetics Innovation Research Institute, Guangzhou 511447, China.
  • 4 Department of Cell Biology, Jinan University, Guangzhou 510632, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China; Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. Electronic address: tydhuang@jnu.edu.cn.
  • 5 Department of Cell Biology, Jinan University, Guangzhou 510632, China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China; Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. Electronic address: yangyan107@jnu.edu.cn.
Abstract

The integrity of the skin barrier is essential for maintaining skin health, with the stratum corneum and filaggrin 2 (FLG-2) playing a key role. FLG-2 deficiency or mutation has been linked to diseases such as atopic dermatitis, while external stressors such as ultraviolet B (UVB) radiation further damage the epidermal barrier. This study investigated the effects of recombinant filaggrin (rFLG) on skin barrier function and UVB induced epidermal destruction. Cell experiments showed that 10 μg/mL of rFLG could increase the mobility of HaCaT cells from 20 % to 42 %, increase the epithelial resistance (TEER) value by about 2 times, and up-regulate the tight junction associated protein by about 2 times. In mouse models of UVB-induced epidermal barrier destruction, rFLG at concentrations of 0.5, 1, and 2 mg/mL showed effective cell uptake and skin penetration, alleviating erythema, and reducing skin thickness in mice by 1.5-3 times. Among them, 2 mg/mL of rFLG treatment restored the expression of tight junction proteins (LOR, ZO-1, and caspase-14), reduced collagen degradation, and reduced oxidative stress by normalizing serum hydroxyproline and superoxide dismutase levels. In addition, 2 mg/mL of rFLG inhibited UVB-induced upregulation of Matrix Metalloproteinases (MMP-3 and MMP-9) and reduced pro-inflammatory factors (IL-10, IL-1α, IL-6, and TNF-α) and apoptotic markers (P38, Bax, and Bcl-2) to normal levels. These findings suggested that rFLG effectively enhanced skin barrier integrity and mitigated UVB-induced epidermal barrier destruction, highlighting its potential as a therapeutic agent for diseases associated with skin barrier dysfunction.

Keywords

Collagen; Recombinant filaggrin-2; Skin barrier; UVB.

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