PMID- 33001866
OWN - NLM
STAT- MEDLINE
DCOM- 20210518
LR  - 20210518
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 5
IP  - 20
DP  - 2020 Oct 15
TI  - Pathogenic and therapeutic role for NRF2 signaling in ultraviolet light-induced 
      skin pigmentation.
LID - 139342 [pii]
LID - 10.1172/jci.insight.139342 [doi]
LID - e139342
AB  - Mottled skin pigmentation and solar lentigines from chronic photodamage with 
      aging involve complex interactions between keratinocytes and melanocytes. 
      However, the precise signaling mechanisms that could serve as therapeutic targets 
      are unclear. Herein, we report that expression of nuclear factor erythroid 
      2-related factor 2 (NRF2), which regulates reduction-oxidation reactions, is 
      altered in solar lentigines and photodamaged skin. Moreover, mottled skin 
      pigmentation in humans could be treated with topical application of the NRF2 
      inducer sulforaphane (SF). Similarly, UV light-induced pigmentation of WT mouse 
      ear skin could be treated or prevented with SF treatment. Conversely, SF 
      treatment was unable to reduce UV-induced ear skin pigmentation in mice deficient 
      in NRF2 or in mice with keratinocyte-specific conditional deletion of IL-6Ralpha. 
      Taken together, NRF2 and IL-6Ralpha signaling are involved in the pathogenesis of 
      UV-induced skin pigmentation, and specific enhancement of NRF2 signaling could 
      represent a potential therapeutic target.
FAU - Kerns, Michelle L
AU  - Kerns ML
FAU - Miller, Robert J
AU  - Miller RJ
FAU - Mazhar, Momina
AU  - Mazhar M
FAU - Byrd, Angel S
AU  - Byrd AS
FAU - Archer, Nathan K
AU  - Archer NK
FAU - Pinkser, Bret L
AU  - Pinkser BL
FAU - Lew, Lance
AU  - Lew L
FAU - Dillen, Carly A
AU  - Dillen CA
FAU - Wang, Ruizhi
AU  - Wang R
FAU - Miller, Lloyd S
AU  - Miller LS
FAU - Chien, Anna L
AU  - Chien AL
FAU - Kang, Sewon
AU  - Kang S
LA  - eng
GR  - R01 AR069502/AR/NIAMS NIH HHS/United States
GR  - R01 AR073665/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20201015
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Il6ra protein, mouse)
RN  - 0 (Isothiocyanates)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Sulfoxides)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Isothiocyanates/pharmacology
MH  - Keratinocytes/pathology/radiation effects
MH  - Melanocytes/pathology/radiation effects
MH  - Mice
MH  - NF-E2-Related Factor 2/*genetics
MH  - Oxidation-Reduction/radiation effects
MH  - Receptors, Interleukin-6/*genetics
MH  - Signal Transduction/drug effects
MH  - Skin Aging/*genetics/pathology/radiation effects
MH  - Skin Pigmentation/*genetics/radiation effects
MH  - Sulfoxides/pharmacology
MH  - Ultraviolet Rays/adverse effects
PMC - PMC7605539
OTO - NOTNLM
OT  - Cellular immune response
OT  - Dermatology
COIS- Conflict of interest: LSM is a full-time employee at Janssen Research and 
      Development. LSM has received grant support from AstraZeneca, MedImmune (a 
      subsidiary of AstraZeneca), Pfizer, Boehringer Ingelheim, Regeneron 
      Pharmaceuticals, and Moderna Therapeutics; is a shareholder of Noveome 
      Biotherapeutics; is a paid consultant for Almirall and Janssen Research and 
      Development; and is on the scientific advisory board of Integrated 
      Biotherapeutics; all of the companies mentioned in this sentence are developing 
      therapeutics against infections and/or inflammatory conditions.
EDAT- 2020/10/02 06:00
MHDA- 2021/05/19 06:00
PMCR- 2020/10/15
CRDT- 2020/10/01 17:15
PHST- 2020/04/20 00:00 [received]
PHST- 2020/09/16 00:00 [accepted]
PHST- 2020/10/02 06:00 [pubmed]
PHST- 2021/05/19 06:00 [medline]
PHST- 2020/10/01 17:15 [entrez]
PHST- 2020/10/15 00:00 [pmc-release]
AID - 139342 [pii]
AID - 10.1172/jci.insight.139342 [doi]
PST - epublish
SO  - JCI Insight. 2020 Oct 15;5(20):e139342. doi: 10.1172/jci.insight.139342.