1. Extracellular Vesicles in Human Skin: Cross-Talk from Senescent Fibroblasts to Keratinocytes by miRNAs
- Author
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Florian Gruber, Dietmar Pum, Lucia Terlecki-Zaniewicz, Michael Mildner, Markus Schosserer, Regina Weinmüllner, Thomas Birngruber, Ingo Lämmermann, Katrin Weiß, Tonja Grillenberger, Eva Stoger, Frédérique Morizot, Elsa Arcalis, Johannes Grillari, Jennifer Schwestka, Thomas Heuser, Erwin Tschachler, Simon Schwingenschuh, Madhusudhan Reddy Bobbili, Ida Perrotta, Vera Pils, and Marlene Brandstetter
- Subjects
Keratinocytes ,0301 basic medicine ,Cell type ,Cellular differentiation ,Blotting, Western ,Human skin ,Cell Communication ,Dermatology ,Biology ,Biochemistry ,Extracellular Vesicles ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,Microscopy, Electron, Transmission ,medicine ,Humans ,Fibroblast ,Molecular Biology ,Cells, Cultured ,Cell Proliferation ,integumentary system ,Cell Differentiation ,Cell Biology ,Extracellular vesicle ,Fibroblasts ,Skin Aging ,Cell biology ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Keratinocyte ,Wound healing - Abstract
Extracellular vesicles (EVs) and their miRNA cargo are intercellular communicators transmitting their pleiotropic messages between different cell types, tissues, and body fluids. Recently, they have been reported to contribute to skin homeostasis and were identified as members of the senescence-associated secretory phenotype of human dermal fibroblasts. However, the role of EV-miRNAs in paracrine signaling during skin aging is yet unclear. Here we provide evidence for the existence of small EVs in the human skin and dermal interstitial fluid using dermal open flow microperfusion and show that EVs and miRNAs are transferred from dermal fibroblasts to epidermal keratinocytes in 2D cell culture and in human skin equivalents. We further show that the transient presence of senescent fibroblast derived small EVs accelerates scratch closure of epidermal keratinocytes, whereas long-term incubation impairs keratinocyte differentiation in vitro. Finally, we identify vesicular miR-23a-3p, highly secreted by senescent fibroblasts, as one contributor of the EV-mediated effect on keratinocytes in in vitro wound healing assays. To summarize, our findings support the current view that EVs and their miRNA cargo are members of the senescence-associated secretory phenotype and, thus, regulators of human skin homeostasis during aging.
- Published
- 2019
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