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- Title
Exosomes derived from human dermal fibroblasts (HDFn‐Ex) alleviate DNCB‐induced atopic dermatitis (AD) via PPARα.
- Authors
Jang, You Na; Lee, Jung Ok; Lee, Jung Min; Park, A. Yeon; Kim, Yu Jin; Kim, Su Young; Seok, Joon; Yoo, Kwang Ho; Kim, Beom Joon
- Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell‐free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast‐neonatal‐derived exosome (HDFn‐Ex) on AD. HDFn‐Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1‐chloro‐2,4‐dinitrobenzene (DNCB)‐mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn‐Ex significantly inhibited DNCB‐induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB‐induced AD‐like mouse model, HDFn‐Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn‐Ex. These effects were blocked by pre‐treatment with GW6471. Furthermore, HDFn‐Ex exhibited an anti‐inflammatory effect by inhibiting the DNCB‐induced increases in IκBα phosphorylation and TNF‐α expression. Collectively, HDFn‐Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn‐Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti‐inflammatory activity.
- Subjects
ATOPIC dermatitis; EXOSOMES; ARTIFICIAL skin; FIBROBLASTS; MAST cells
- Publication
Experimental Dermatology, 2024, Vol 33, Issue 1, p1
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.14970