Dataset Information

Lipid metabolism dysregulation in solar lentigo: a multi-system-level analysis reveals membrane instability and energy homeostasis disruption

ABSTRACT: Solar lentigo is a common hyperpigmented skin condition caused by chronic ultraviolet exposure, primarily affecting photoaged skin. While previous investigations focused on inflammatory and melanogenic mechanisms, the comprehensive role of lipid metabolism in pathogenesis remains unclear. We aimed to investigate systemic alterations in lipid metabolism and their contribution to solar lentigo development. We performed comprehensive analysis of RNA sequencing data from solar lentigo lesions and control skin samples (n=7 per group) using metabolic flux simulations, gene co-expression networks, and protein-protein interaction analysis. These multi-system approaches were integrated to identify coordinated alterations in lipid metabolic pathways. Solar lentigo samples exhibited coordinated inhibition of fatty acid elongation, acetyl-CoA carboxylase activity, and sphingolipid biosynthesis, alongside impaired cholesterol synthesis via reduced squalene epoxidase and 7-dehydrocholesterol reductase activity. Compensatory upregulation of phospholipid synthesis enzymes and dihydroceramide desaturases was observed. Pathway disruption and altered calcium signaling, indicating aberrant cellular energy metabolism and membrane integrity. These findings demonstrate that solar lentigo pathogenesis involves systematic lipid metabolism dysregulation beyond melanogenesis, causing membrane instability, energy homeostasis disruption and redox imbalance. The identification of specific metabolic bottlenecks reveals novel targets for lipid-based therapeutic approaches in pigmentary diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE318414 | GEO | 2026/02/06

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:We here present a novel subtype of fibroblasts isolated from sun-exposed skin of elderly donors and characterized by its prominent and stable myo-chondrocyte-type differentiation. As we depict a similar chondrocyte-type expression pattern at sites of solar elastosis in human skin, we propose that this fibroblasts phenotype develops in the course of massive and perseverative UV-dependent damage as part of the process terminating in the most severe appearance of photoaging - solar elastosis. Along with the abnormal expression profile, these “old” fibroblasts generate a chondrocyte-type matrix with a layer of myofibroblast-differentiation in close vicinity to the epidermis, when propagated as skin equivalents (SEs) in 3D organotypic cultures. Importantly, these fibroblasts are strongly reduced in their ability to support epidermal growth and differentiation, allowing for rapid/premature epidermal atrophy. Having identified TGFß as an important player in this scenario, we show that the addition of TGFß to normal young fibroblast induces while inhibition of TGFß to the old fibroblast abolishes the myo-chondrogenic expression profile. Accordingly, inhibiting TGFß in the in vivo-like SEs, not only abrogates the aberrant phenotype but allows these fibroblasts to regain their normal mutual interaction with the epidermal keratinocytes and to support epidermal regeneration and longevity. Further, we provide evidence for a role of chronic solar UV radiation in initiating chondrogenic gene expression in young fibroblasts. Concomitantly, we show however, that the same UV treatment abolishes myofibroblast differentiation in the SEs with the “old” chondrogenic fibroblasts, and that this selective inhibition is already sufficient to restore the fibroblasts’ ability for successfully supporting epidermal growth and differentiation. From this it is tempting to suggest, that besides all damaging potential, “mild” solar UV radiation may exert also beneficial effects, e.g. in promoting activation of photoaged skin.

Dataset Information

Lipid metabolism dysregulation in solar lentigo: a multi-system-level analysis reveals membrane instability and energy homeostasis disruption

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets