Project description:Skin aging caused by UV is called photoaging, which is characterized by deeper wrinkles accompanied by senescence of dermal fibroblasts and reduction of collagens. Rice fermentation, widely used in the cosmetics, has been reported to possess anti-aging benefits on skincare, however, its roles in the skin photoaging remains unclear. In this study, the effects of Maifuyin (a rice fermentation), and its ingredients succinic acid (SA) and choline on UVA-induced senescence in fibroblasts were evaluated. A mRNA sequencing technology (RNA-seq) was applied to study the effects of these ingredients on UVA-induced photoaging. In conclusion, these results highlight the potential use of Maifuyin and SA as promising agents for anti-photoaging applications.
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.
Project description:Background: Skin aging can be classified into intrinsic and extrinsic types, with photoaging representing a significant form of extrinsic aging. Photoaging is caused by prolonged exposure to ultraviolet (UV) radiation, resulting in cellular damage, collagen degradation, and the development of wrinkles and pigmentation changes; severe cases can even lead to skin cancer. This condition affects individual aesthetics and health and imposes a broader societal burden, including increased healthcare costs and reduced quality of life. Addressing photoaging is critical, as effective treatments can enhance skin health, improve mental well-being, and alleviate the burden on healthcare systems, highlighting the importance of preventive and therapeutic strategies. Objective: This study aimed to develop a novel drug based on human type III collagen mRNA (hCOL3A1 mRNA) and to investigate its role in treating UVB-induced skin photoaging. Methods: We designed and synthesized the complete hCOL3A1 mRNA sequence and encapsulated it in lipid nanoparticles for skin delivery. The expression of the hCOL3A1 mRNA drug in human fibroblasts was examined by in vitro experiments, and its potential therapeutic effects on UVB-induced aging, oxidative stress, and inflammation were evaluated. In addition, we evaluated the efficacy of the hCOL3A1 mRNA drug on UVB-induced skin photoaging by an in vivo model. Results: It was found that the hCOL3A1 mRNA drug was effective in reducing UVB-induced skin photoaging, suggesting that the hCOL3A1 mRNA drug could be used as a therapeutic intervention for UVB-induced photoaging and also providing a novel approach to restore aging skin by increasing endogenous collagen production and reducing oxidative and inflammatory damage Conclusion: hCOL3A1 mRNA-LNP, as a novel protein therapeutic approach, overcomes the limitations of retinoic acid (RA) therapy, provides a simpler and more efficient therapeutic option, and is expected to be a new treatment for skin photoaging.
Project description:Photoaging results from the damaging effects of long-term exposure to UV. It is characterized by deep wrinkle, but the mechanism is still lack. To better understand molecular events contributing to photoaging, We used microarray analysis using an optimized in time-dependent wrinkle model in mice.
Project description:Human skin is composed of the cell-rich epidermis, the extracellular matrix (ECM) rich dermis, and the hypodermis. Within the dermis, a dense network of ECM proteins provides structural support to the skin and regulates a wide variety of signaling pathways which govern cell proliferation and other critical processes. Both intrinsic aging, which occurs steadily over time, and extrinsic aging (photoaging), which occurs as a result of external insults such as UV radiation, cause alterations to the dermal ECM. In this study, we utilized both quantitative and global proteomics, alongside single harmonic generation (SHG) and two-photon autofluorescence (TPAF) imaging, to assess changes in dermal composition during intrinsic and extrinsic aging. We find that both intrinsic and extrinsic aging result in significant decreases in structural ECM integrity, evidenced by decreasing collagen abundance and increasing fibril fragmentation, and ECM-supporting proteoglycans. Intrinsic aging also produces changes distinct from those produced by photoaging, including reductions in elastic fiber and crosslinking enzyme abundance. In contrast, photoaging is primarily defined by increases in elastic fiber-associated protein and pro-inflammatory proteases. Changes induced by photoaging are evident even in comparisons of young underarm and forearm skin, indicating that photoexposure experienced by an individual’s mid-20s is sufficient for large-scale proteomic alterations and that molecular-level changes due to photoaging are evident well before clinical indications are present. GO term enrichment revealed that both intrinsic aging and photoaging share common features of chronic inflammation.
Project description:Photoaging is cumulative damage that is caused by chronic, repeated solar radiation exposure to skin. Its molecular mechanisms are poorly understood at the level of global gene expression.This study set out to uncover genes and functional modules involved in photoaging at the level of transcription, with the use of skin samples from Chinese women.Using the Illumina microarray platform, we compared the genome-wide expression profiles of 21 pairs of sun-exposed pre-auricular and sun-protected post-auricular skin samples from northern Chinese women.In total, 1,621 significantly regulated genes were identified from skin due to photoaging by microarray analysis. These genes were subjected to functional enrichment analyses with both the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation databases. As revealed by the functional analyses, the up-regulated functional modules in sun-exposed pre-auricular skin were related to various cellular activities in regulation of the skin homeostasis (e.g., the KEGG pathways TGF-beta signaling pathway and ECM-receptor interaction ), whereas the down-regulated functional modules were mostly metabolic-related. Additionally, five selected genes (HOXA5, LEPR, CLDN5, LAMC3, and CGA) identified as differentially-expressed were further confirmed on their expression by quantitative real-time PCR (Q-RT-PCR). Our findings suggest that damage from skin homeostasis and down-regulation of skin metabolism may play important roles in the process of photoaging. We compared the genome-wide expression profiles of 21 pairs of sun-exposed pre-auricular and sun-protected post-auricular skin samples from northern Chinese women by using the Illumina microarray platform.