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Study on the Effects of Retinoids on UVR-Induced Skin Photoaging [Spatial Transcriptomics]

ABSTRACT: Photoaging contributes to up to 80% of visible facial aging signs, making it a major dermatological concern. While retinoids such as retinol and all-trans retinoic acid (ATRA) promote extracellular matrix (ECM) regeneration, their side effects limit widespread use. We propose that hydroxypinacolone 9-cis retinoate (9-cis HPR), a derivative of 9-cis retinoic acid, activates both retinoic acid receptor (RAR) and retinoid X receptor (RXR), enhancing efficacy while minimizing irritation. However, its in vivo anti-photoaging effects remain underexplored. This study evaluates 9-cis HPR in the UVR-damaged SKH-1 mouse model, investigating its role in inflammation control, ECM regeneration, and melanogenesis suppression.

ORGANISM(S): Mus musculus

PROVIDER: GSE294120 | GEO | 2026/01/20

REPOSITORIES: GEO

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Study on the Effects of Retinoids on UVR-Induced Skin Photoaging [scRNA-seq]

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Project description:Background: N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. Objectives: This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. Methods: m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. Results: m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-R and upregulation of MMP1 in UVR-irradiated HDFs. Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. Conclusions: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

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