The authors focus on how neurohormones impact human skin physiology and pathology. They highlight basic concepts, major open questions, and translational research perspectives in cutaneous neuroendocrinology and argue that greater emphasis on neuroendocrine human skin research will foster the development of novel dermatological therapies.
[Trends in Molecular Medicine]
Investigators showed that NRF2 suppressed the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers.
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Jessen, C., Kreß, J. K. C., Baluapuri, A., Hufnagel, A., Schmitz, W., Kneitz, S., Roth, S., Marquardt, A., Appenzeller, S., Ade, C. P., Glutsch, V., Wobser, M., Friedmann-Angeli, J. P., Mosteo, L., Goding, C. R., Schilling, B., Geissinger, E., Wolf, E., & Meierjohann, S. (2020). The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01477-8 Cite
Investigators uncovered COL17 as a binding partner of the aPKC‐PAR complex, which is a key regulating factor of cell polarity. Immunoprecipitation‐immunoblot assay and protein‐protein binding assay revealed that COL17 interacts with aPKC and PAR3. Type XVII collagen (COL17) deficiency or epidermis‐specific aPKCλ deletion destabilized PAR3 distribution in the epidermis, while aPKCζ knockout did not.
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Watanabe, M., Kosumi, H., Osada, S.-I., Takashima, S., Wang, Y., Nishie, W., Oikawa, T., Hirose, T., Shimizu, H., & Natsuga, K. (n.d.). Type XVII collagen interacts with the aPKC-PAR complex and maintains epidermal cell polarity. Experimental Dermatology, n/a(n/a). https://doi.org/10.1111/exd.14196 Cite
Scientists describe optimization of current methods and present new protocols for using human papillomavirus capsids to deliver non-viral DNA, thereby providing an alternative to DNA transfection. Using keratinocyte generated extracellular matrices could enhance infection efficiency in keratinocytes, hepatocytes and neuronal cells.
Adult scalp dermal progenitor cells and epidermal stem cells together with type I collagen as a scaffold material were used to reconstitute bilayer tissue-engineered skin substitutes in vitro.
[Stem Cell Research & Therapy]
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Zhang, Q., Wen, J., Liu, C., Ma, C., Bai, F., Leng, X., Chen, Z., Xie, Z., Mi, J., & Wu, X. (2020). Early-stage bilayer tissue-engineered skin substitute formed by adult skin progenitor cells produces an improved skin structure in vivo. Stem Cell Research & Therapy, 11(1), 407. https://doi.org/10.1186/s13287-020-01924-z Cite
Using cytokine array screening, scientists found that autophagy deficiency inhibited the transcription and production of the cytokine CCL2/MCP-1 by TNF.
The authors investigate the association of exosomes with vitiligo and emphasize the role of exosomes in immune regulation, melanocyte–keratinocyte interactions, and melanogenesis.
The authors showed that melanocyte survival was mediated by diverse, nonredundant signaling pathways, including ERK1/2, AKT, PKA, and PKC.
Investigators elucidated the significance of exosome in keratinocyte-macrophage crosstalk following injury.
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Zhou, X., Brown, B. A., Siegel, A. P., El Masry, M., Zeng, X., Song, W., Das, A., Khandelwal, P., Clark, A., Singh, K., Guda, P. R., Gorain, M., Timsina, L., Xuan, Y., Jacobson, S. C., Novotny, M. V., Roy, S., Agarwal, M., Lee, R. J., … Ghatak, S. (2020). Exosome-Mediated Crosstalk between Keratinocytes and Macrophages in Cutaneous Wound Healing. ACS Nano. https://doi.org/10.1021/acsnano.0c03064 Cite
Among direct Notch target genes were multiple DNA damage response genes, including IER5, which researchers showed were required for Notch-induced differentiation of squamous carcinoma cells and TERT-immortalized keratinocytes.
Investigators performed methylation loci fine-mapping to search the top signals in the entire CYP2S1 gene region, and further carried out gene expression assay, cell proliferation, apoptosis, differentiation and migration in CYP2S1 overexpressed (CYP2S1over) and silenced human keratinocytes.
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