PMID- 37975541
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240206
IS  - 1600-0625 (Electronic)
IS  - 0906-6705 (Linking)
VI  - 33
IP  - 1
DP  - 2024 Jan
TI  - Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced 
      atopic dermatitis (AD) via PPARalpha.
PG  - e14970
LID - 10.1111/exd.14970 [doi]
AB  - 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 alpha (PPARalpha) 
      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 
      PPARalpha 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 PPARalpha. 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 PPARalpha, 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 IkappaBalpha phosphorylation and TNF-alpha 
      expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, 
      these effects were regulated by PPARalpha. 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.
CI  - (c) 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Jang, You Na
AU  - Jang YN
AUID- ORCID: 0000-0002-0014-9783
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
FAU - Lee, Jung Ok
AU  - Lee JO
AUID- ORCID: 0000-0002-0048-5322
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
FAU - Lee, Jung Min
AU  - Lee JM
AUID- ORCID: 0000-0002-4670-2521
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
FAU - Park, A Yeon
AU  - Park AY
AUID- ORCID: 0000-0002-4667-8875
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
AD  - Department of Dermatology, Chung-Ang University College of Medicine, Seoul, South 
      Korea.
FAU - Kim, Yu Jin
AU  - Kim YJ
AUID- ORCID: 0000-0002-1247-2887
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
AD  - Department of Dermatology, Chung-Ang University College of Medicine, Seoul, South 
      Korea.
FAU - Kim, Su Young
AU  - Kim SY
AUID- ORCID: 0000-0002-3251-5813
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
AD  - Department of Dermatology, Chung-Ang University College of Medicine, Seoul, South 
      Korea.
FAU - Seok, Joon
AU  - Seok J
AUID- ORCID: 0000-0002-8016-8385
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
AD  - Department of Dermatology, Chung-Ang University College of Medicine, Seoul, South 
      Korea.
FAU - Yoo, Kwang Ho
AU  - Yoo KH
AUID- ORCID: 0000-0002-0137-6849
AD  - Department of Dermatology, Chung-Ang University Gwang-Myeong Hospital, Chung-Ang 
      University College of Medicine, Seoul, South Korea.
FAU - Kim, Beom Joon
AU  - Kim BJ
AUID- ORCID: 0000-0003-2320-7621
AD  - Department of Medicine, Graduate School, Chung-Ang University, Seoul, South 
      Korea.
AD  - Department of Dermatology, Chung-Ang University College of Medicine, Seoul, South 
      Korea.
LA  - eng
GR  - Chung-Ang University Research Scholarship Grants/
GR  - 2021R1G1A1007827/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20231117
PL  - Denmark
TA  - Exp Dermatol
JT  - Experimental dermatology
JID - 9301549
RN  - 0 (PPAR alpha)
RN  - 0 (Dinitrochlorobenzene)
RN  - 0 (Filaggrin Proteins)
RN  - 0 (Dinitrobenzenes)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Infant, Newborn
MH  - Humans
MH  - *Dermatitis, Atopic/chemically induced/drug therapy/metabolism
MH  - PPAR alpha/metabolism
MH  - Dinitrochlorobenzene/metabolism/pharmacology/therapeutic use
MH  - Filaggrin Proteins
MH  - Dinitrobenzenes/adverse effects/metabolism
MH  - *Exosomes/metabolism
MH  - Skin/metabolism
MH  - Anti-Inflammatory Agents/pharmacology
MH  - *Skin Diseases/metabolism
MH  - Cytokines/metabolism
MH  - Mice, Inbred BALB C
OTO - NOTNLM
OT  - PPARalpha
OT  - atopic dermatitis
OT  - dermal fibroblast
OT  - exosomes
OT  - filaggrin
OT  - keratinocyte
OT  - skin barrier
EDAT- 2023/11/17 15:24
MHDA- 2024/01/30 12:43
CRDT- 2023/11/17 07:23
PHST- 2023/07/30 00:00 [revised]
PHST- 2023/04/16 00:00 [received]
PHST- 2023/09/04 00:00 [accepted]
PHST- 2024/01/30 12:43 [medline]
PHST- 2023/11/17 15:24 [pubmed]
PHST- 2023/11/17 07:23 [entrez]
AID - 10.1111/exd.14970 [doi]
PST - ppublish
SO  - Exp Dermatol. 2024 Jan;33(1):e14970. doi: 10.1111/exd.14970. Epub 2023 Nov 17.