TY - JOUR
T1 - ZFP750 affects the cutaneous barrier through regulating lipid metabolism
AU - Butera, Alessio
AU - Agostini, Massimiliano
AU - Cassandri, Matteo
AU - De Nicola, Francesca
AU - Fanciulli, Maurizio
AU - D’Ambrosio, Lorenzo
AU - Falasca, Laura
AU - Nardacci, Roberta
AU - Wang, Lu
AU - Piacentini, Mauro
AU - Knight, Richard A.
AU - Jia, Wei
AU - Sun, Qiang
AU - Shi, Yufang
AU - Wang, Ying
AU - Candi, Eleonora
AU - Melino, Gerry
N1 - Funding information:
This work has been supported primarily by the MUR-PNRR (M4C2I1.3 PE6 project PE00000019 Heal Italia CUP: E83C22004670001) (to E.C., G.M., and M.A.). This work has also been supported by Associazione Italiana per la Ricerca contro il Cancro (AIRC) IG#20473 (2018–2022) and IG 2022 ID 27366 (2023–2027) (to G.M.), AIRC IG#22206 (2019–2023) (to E.C.), Fondazione Luigi Maria Monti IDI-IRCCS ricerca corrente (to E.C.), Ministry of Health & MAECI Italy-China Science and Technology Cooperation PGR00961 (to E.C.), The National Key R&D Program of China 2022YFA0807300 (to Y.W.), Regione Lazio through LazioInnova Progetto Gruppo di Ricerca n 85-2017-14986 (n 33 & n 55-2021-T0002E0001; to G.M. and E.C.), Progetti di Ricerca Scientifica d’Ateneo CUP:E83C22001850005 (to M.A.), and CAMS Innovation Fund for Medical Sciences 2021-I2M-5-008 (to Q.S.).
Publisher Copyright:
© 2023 The Authors, some rights reserved
PY - 2023/4/28
Y1 - 2023/4/28
N2 - An essential function of the epidermis is to provide a physical barrier that prevents the loss of water. Essential mediators of this barrier function include ceramides, cholesterol, and very long chain fatty acids, and their alteration causes human pathologies, including psoriasis and atopic dermatitis. A frameshift mutation in the human ZNF750 gene, which encodes a zinc finger transcription factor, has been shown to cause a seborrhea-like dermatitis. Here, we show that genetic deletion of the mouse homolog ZFP750 results in loss of epidermal barrier function, which is associated with a substantial reduction of ceramides, nonpolar lipids. The alteration of epidermal lipid homeostasis is directly linked to the transcriptional activity of ZFP750. ZFP750 directly and/or indirectly regulates the expression of crucial enzymes primarily involved in the biosynthesis of ceramides. Overall, our study identifies the transcription factor ZFP750 as a master regulator epidermal homeostasis through lipid biosynthesis and thus contributing to our understanding of the pathogenesis of several human skin diseases.
AB - An essential function of the epidermis is to provide a physical barrier that prevents the loss of water. Essential mediators of this barrier function include ceramides, cholesterol, and very long chain fatty acids, and their alteration causes human pathologies, including psoriasis and atopic dermatitis. A frameshift mutation in the human ZNF750 gene, which encodes a zinc finger transcription factor, has been shown to cause a seborrhea-like dermatitis. Here, we show that genetic deletion of the mouse homolog ZFP750 results in loss of epidermal barrier function, which is associated with a substantial reduction of ceramides, nonpolar lipids. The alteration of epidermal lipid homeostasis is directly linked to the transcriptional activity of ZFP750. ZFP750 directly and/or indirectly regulates the expression of crucial enzymes primarily involved in the biosynthesis of ceramides. Overall, our study identifies the transcription factor ZFP750 as a master regulator epidermal homeostasis through lipid biosynthesis and thus contributing to our understanding of the pathogenesis of several human skin diseases.
UR - http://www.scopus.com/inward/record.url?scp=85159243686&partnerID=8YFLogxK
U2 - 10.1126/SCIADV.ADG5423
DO - 10.1126/SCIADV.ADG5423
M3 - Journal article
C2 - 37115925
AN - SCOPUS:85159243686
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 17
M1 - eadg5423
ER -
