Phototherapy represents an attractive route for treating a range of challenging dermatological diseases. Existing skin phototherapy modalities rely on direct UV illumination, although with limited efficacy in addressing disorders of deeper tissue and with requirements for specialized illumination equipment and masks to shield unaffected regions of the skin. This work introduces a skin‐integrated optoelectronic device that incorporates an array of UVA (360 nm) light emitting diodes in layouts that match those of typical lesional plaques and in designs that couple to biocompatible, penetrating polymer microneedle light waveguides to provide optical access to deep skin. Monte Carlo simulations and experimental results in phantom skin suggest that these waveguides significantly enhance light delivery to deep skin, with a >4‐fold increase for depths of >500 µm. In ex vivo human skin, the devices show reduced measures of phototoxicity compared to direct illumination and enhanced modulation of gene expression relevant to sclerosing skin diseases. These systems are also compatible with design principles in soft, skin‐compatible electronics and battery‐powered wireless operation. Collectively, the favorable mechanical and light delivery properties of these devices expand possibilities in targeting of deep skin lesions beyond those attainable with clinical‐standard UV light therapy approaches.
We have shown that microRNAs-103 and -107 (miRs-103/107) positively regulate end-stage autophagy by ensuring dynamin activity in cultured keratinocytes. Most work in end-stage autophagy has been conducted using in vitro model systems. In vivo regulation of end-stage autophagy in epidermis remains unknown. Here, we used antagomirs to subcutaneously knock down miR-107 in the skin; conversely, we delivered miR-107 mimic subcutaneously via in vivo transfection to increase this miR. We found that antagomir-107 treatment in epidermis: (i) depleted endogenous miR-107; (ii) increased GFP-LC3 puncta in epidermal basal layers of GFP-LC3 transgenic mice, indicative of an accumulation of autophagosomes; (iii) inhibited LC3 turnover and increased p62, suggesting an inhibition of autophagy flux; and (iv) increased phosphorylated dynamin (p-dynamin, an inactive form), a key enzyme in end-stage autophagy. Conversely, miR-107 mimic treatment in mouse epidermis: decreased GFP-LC3 puncta in basal layer, as well as p62 protein levels; and diminished p-dynamin, indicative of activation of this enzyme. In human epidermal keratinocytes, antagos-103/107 cause the formation of large vacuoles and an increase in p-dynamin, which can be rescued by inhibition of protein kinase C pathway. Collectively, these results suggest that the miR-103/107 family has a critical role in regulating end-stage autophagy in mouse epidermis via PLD1/2-protein kinase C-dynamin pathway.
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