Single-Cell Atlas of Photoaged Skin Reveals JAK-STAT Blockade as a Strategy to Reverse Dermal Remodeling
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE334230 | GEO | 2026/06/10
REPOSITORIES: GEO
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Project description:Ultraviolet (UV) radiation from the sun causes adverse skin changes such as premature aging. UV-induced mitochondrial DNA (mtDNA) alterations, including deletions, contribute to photoaging and cellular dysfunction. The most frequent mtDNA rearrangement is the common deletion (CD), characterized by the loss of nearly one-third of the genome (4,977 bp). Although UV radiation exposure leads to CD formation, the molecular mechanisms initiating UV-induced CD remain poorly defined. In this study, we show that increasing UV doses increase CD levels in human skin fibroblasts. UVA exposure increased cellular reactive oxygen species (ROS) and mtDNA oxidation. Antioxidant preconditioning prevented UVA-induced CD accumulation, indicating a ROS-dependent mechanism. Conversely, UVB exposure induced cyclobutane pyrimidine dimers (CPDs) without affecting ROS, suggesting a ROS-independent pathway. Using a 3D full-thickness human skin model, we confirmed UVA-dependent CD formation in both epidermis and dermis. RNA-Seq analysis of UVA-exposed fibroblasts revealed upregulation of mitochondrial DNA replication genes and downregulation of mtDNA repair genes. Taken together, our findings provide insight into how UVA and UVB differ in their detrimental effects on mtDNA, with UVA impacting mtDNA maintenance and transcription via a ROS-dependent mechanism.
2025-11-30 | GSE302943 | GEO
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.
2025-03-01 | GSE284483 | GEO
Project description:The UVB component of the sunlight (290-320 nm) plays an important role in carcinogenesis through generation of high levels of bipyrimidine DNA photoproducts, while UVA (320-400 nm) has been associated with photoaging and tumor progression through generation of low, but continuous levels of DNA damage and oxidative stress. However, the contribution of UVA light to epidermal cell fate in the context of photoaging remains poorly understood. Here, by using proteomic analyses and biochemical assays for validation, we show that UVA induces proteome remodeling and senescence in primary keratinocytes, eliciting potent antioxidant and pro-inflammatory responses. As a model of early skin tumorigenesis during aging, immortalized non-malignant keratinocytes, bearing potentially oncogenic mutations and dysfunctional components of the senescent machinery , are resilient to UVA-induced stress, but are sensitive to paracrine oxidative stress and immune system activation induced by senescent neighboring keratinocytes. These observations reveal a new cellular mechanism by which UVA induces photoaging in the epidermis.
2022-02-17 | PXD025191 | Pride
Project description:To test whether there is a photoprotective benefit after different types of suberythemal repetitive UV, a 1.5 MED challenge dose was applied 1 week after the initial 2 weeks of repetitive irradiation. To determine what different mechanisms and/or factors might be involved in physiological pigmentary responses of the skin to different types of UV, we used whole human genome microarrays and immunohistochemical analyses to characterize human skin in situ to examine how melanocyte-specific proteins and paracrine melanogenic factors are regulated by repetitive exposure to suberythemal doses of different types of UV (UVA and/or UVB). Seven volunteers with skin type II-III were irradiated with UVA, UVB or UVA+UVB radiation for 2 weeks (5 times per week, 10 times total) after preliminary determination of their MEDs. A UVA+UVB challenge dose of 1.5X the MED was applied 1 week later. Biopsies were taken before the challenge dose, immediately after the challenge dose, 4 days after the challenge, and 15 weeks after the challenge.
2014-12-12 | E-GEOD-56754 | biostudies-arrayexpress
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.
2014-07-14 | GSE58915 | GEO
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.
2023-08-10 | GSE240226 | GEO
Project description:Ultraviolet (UV) wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, while higher doses protect from UVB immunosuppression in mice. We have previously shown that these responses to UVA are genetically restricted as they occur in C57BL/6 but not Balb/c mice. We used gene set enrichment analysis of microarray data and real-time RT-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found up-regulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from down regulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting previous identification of IL-12 and IL-10 in high dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin. 24 hours after UVA, UVB and ssUV irradiation, a 1 cm2 uniform section of skin was excised from the dorsal surface of irradiated and control mice. Total RNA was then extracted from the whole skin using TRIzol reagent (Gibco Invitrogen Life Technologies, Carlsbad, CA, USA) according to the manufacturerâ??s instructions, purified, DNase treated and reverse transcribed into cDNA. For the microarray study a direct incorporation of Cyanine 3-dCTP and Cyanine 5-dCTP fluorescent dyes (Perkin Elmer Life Sciences, Inc. Boston, MA, USA) was used for cDNA synthesis. For each UV dose, a reference design was used to compare an unirradiated control against an irradiated sample. Microarray experiments used compugen 22k mouse oligonucleotide microarray slides (The Clive and Vera Ramaciotti Centre for Gene Function Analysis, Sydney Australia (http://www.ramaciotti.unsw.edu.au). Lower and higher UVA doses were used. C57BL/6 mice were irradiated with lower UVA, higher UVA, UVB, or ssUV; Balb/C mice were irradiated with lower or higher UVA. Experiments were replicated 6 times for each UV dose. A fluorescent dye swap was done for each alternate hybridisation to reduce systematic dye bias of incorporated fluorescent dyes.
2010-05-16 | E-GEOD-15618 | biostudies-arrayexpress
Project description:To test the hypothesis that different mechanisms and/or factors might be involved in physiological pigmentary responses of the skin to different types of UV, we used whole human genome microarrays and immunohistochemical analyses to characterize human skin in situ to examine how melanocyte-specific proteins and paracrine melanogenic factors are regulated by repetitive exposure to suberythemal doses of different types of UV (UVA, UVB or SSR). Six volunteers with skin type II-III were irradiated with SSR, UVA or UVB radiation for 2 weeks (5 times per week, 10 times total) after preliminary determination of their MEDs. Biopsies were taken 3 days after the last irradiation.
2010-08-18 | E-GEOD-21429 | biostudies-arrayexpress
Project description:Ultraviolet (UV) wavebands in sunlight are immunomodulatory. About half the amount of UVA within a minimum erythemal dose of sunlight is systemically immunosuppressive, while higher doses protect from UVB immunosuppression in mice. We have previously shown that these responses to UVA are genetically restricted as they occur in C57BL/6 but not Balb/c mice. We used gene set enrichment analysis of microarray data and real-time RT-PCR confirmation to determine the molecular mechanisms associated with UVA immunomodulation. We found up-regulation of mRNA for the alternative complement pathway. The core-enriched genes complement component 3, properdin and complement factor B were all activated by the immunosuppressive dose of UVA only in UVA-responsive C57BL/6 but not unresponsive BALB/c mice. This therefore matched the genetic restriction and dose responsiveness of UVA immunosuppression. The immune-protective higher UVA dose prevented UVB from down regulating chemokine receptor 7 and IL-12B, and decreased IL-10, supporting previous identification of IL-12 and IL-10 in high dose UVA protection from UVB immunosuppression. Our study has identified activation of the alternative complement pathway as a trigger of UVA-induced systemic immunosuppression and suggests that this pathway is likely to be an important sensor of UVA-induced damage to the skin.
2009-06-29 | GSE15618 | GEO
Project description:Here we investigated the effects of JAK/STAT pharmacological inhibition on cHL cell models using ruxolitinib, a JAK 1/2 inhibitor. We use five classical Hodgkin lymphoma cell lines: L428, L1236, L540, KMH2, L591
2021-10-15 | GSE185818 | GEO