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Fibroblast heterogeneity: a new phenotype associated with photoaging/solar elastosis

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200002 | GEO | 2023/03/22

REPOSITORIES: GEO

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Project description:UV radiation (UV) alters secondary metabolism in the skin of Vitis vinifera L. berries, which may affect on the final composition of both, grapes and wines. We compared berry skin transcriptome and phenolic composition between Tempranillo berries grown in the presence or absence of solar UV in a mid-altitude Tempranillo vineyard. By analysing two different ripening degrees, expression of 121 genes was significantly altered. Functional enrichment identified that, principally, secondary metabolism-related transcripts were induced by UV, including VvFLS1, VvGT5 and VvGT6 flavonol biosynthetic genes induction. Concurrently, flavonol accumulation was the most evident impact of UV on the berry skin phenolic composition. Monoterpenoid biosynthetic transcripts were also up-regulated by UV, whereas induction of stilbenoid biosynthetic transcripts and stilbenes accumulation was probably induced by the joint action of UV and other condition under the UV-blocking filter, likely higher temperature. Among regulatory genes, VvMYBF1, VvMYB24 and three bHLH transcription factors were up-regulated by UV. Homologs to Arabidopsis UVR8-dependent UV-B-induced genes were also induced, including VvHY5-1, VvHY5-2 and VvRUP UV-B signalling genes. This suggests that the UV-B-specific signalling pathway is activated in the skin of grapes grown at low-medium altitudes. The biosynthesis and accumulation of UV-absorbing compounds that are appreciated for winemaking were almost specifically triggered, which indicates that viticultural practices increasing solar UV incidence may improve grape features important to wine production. A total of 12 samples were hybridized. Grape skin RNA from berries ripening under a UV-transmitting filter (FUV+) and a UV-blocking filter (FUV-) was compared. Berry skin of two different ripening stages was analysed on each UV treatment. All samples were harvested simultaneously and a NaCl series was used to select the ripening degree in a non-invasive way. Three biological replicates were analyzed for each sample.

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Fibroblast heterogeneity: a new phenotype associated with photoaging/solar elastosis

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