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
  • 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: [email protected].
  • 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: [email protected].
PMID: 39341309 DOI: 10.1016/j.ijbiomac.2024.136064
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.
Products
Inhibitors & Agonists
Other Products