WTAP-Mediated N6-Methyladenosine of RNAs Facilitate the Pathophysiology of Atopic Dermatitis

Lina Tan; Xue Chen; Siyu Yan; Aiyuan Guo; Lihua Gao; Lu Zhou; Yanping Zhou; Jinrong Zeng; Jianyun Lu

doi:10.1016/j.jid.2023.10.032

WTAP-Mediated N6-Methyladenosine of RNAs Facilitate the Pathophysiology of Atopic Dermatitis

J Invest Dermatol. 2024 May;144(5):1058-1070.e4. doi: 10.1016/j.jid.2023.10.032. Epub 2023 Nov 27.

Authors

Lina Tan¹, Xue Chen¹, Siyu Yan¹, Aiyuan Guo¹, Lihua Gao¹, Lu Zhou¹, Yanping Zhou², Jinrong Zeng³, Jianyun Lu⁴

Affiliations

¹ Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, China; Medical Ozone Research Center, Central South University, Changsha, China.
² Department of Operating Room, Third Xiangya Hospital, Central South University, Changsha, China.
³ Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, China; Medical Ozone Research Center, Central South University, Changsha, China. Electronic address: zengjinrong1989@csu.edu.cn.
⁴ Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, China; Medical Ozone Research Center, Central South University, Changsha, China. Electronic address: xiaoyun3@csu.edu.cn.

PMID: 38029838
DOI: 10.1016/j.jid.2023.10.032

Abstract

N6-methyladenosine (m⁶A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m⁶A-mRNA epitranscriptomic microarray to screen for differentially expressed genes and their m⁶A levels and m⁶A-related enzymes in patients with AD. We confirmed that the m⁶A RNA methyltransferase WTAP and 2 candidate differentially expressed genes (S100A9 and SERPINB3) were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD. In vitro cell experiments confirmed that WTAP influenced the expression of the 2 candidate differentially expressed genes and promoted primary human epidermal keratinocyte proliferation while inhibiting human epidermal keratinocyte differentiation. Furthermore, we showed that WTAP, S100A9, and SERPINB3 expression correlated with AD severity. Our findings revealed that WTAP-mediated m⁶A modification promoted the expression of S100A9 and SERPINB3 to aggravate human epidermal keratinocyte proliferation and dysdifferentiation contributing to the pathophysiological development of AD.

Keywords: Atopic dermatitis; S100A9; SERPINB3; WTAP; m(6)A modification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine* / analogs & derivatives*
Adenosine* / metabolism
Calgranulin B / genetics
Calgranulin B / metabolism
Cell Cycle Proteins*
Cell Differentiation / genetics
Cell Proliferation* / genetics
Cells, Cultured
Dermatitis, Atopic* / genetics
Dermatitis, Atopic* / metabolism
Dermatitis, Atopic* / pathology
Epidermis / metabolism
Epidermis / pathology
Female
Humans
Keratinocytes* / metabolism
Male
Methyltransferases* / genetics
Methyltransferases* / metabolism
RNA Splicing Factors*
RNA, Messenger / genetics
RNA, Messenger / metabolism

Substances

N-methyladenosine
Adenosine
Methyltransferases
WTAP protein, human
Calgranulin B
S100A9 protein, human
RNA, Messenger
RNA Splicing Factors
Cell Cycle Proteins