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Keratinocyte Microvesicles Regulate the Expression of Multiple Genes in Dermal Fibroblasts




TekijätPing Huang, Jiarui Bi, Gethin R. Owen, Weimin Chen, Anne Rokka, Leeni Koivisto, Jyrki Heino, Lari Häkkinen, Hannu Larjava

KustantajaNATURE PUBLISHING GROUP

Julkaisuvuosi2015

JournalJournal of Investigative Dermatology

Tietokannassa oleva lehden nimiJOURNAL OF INVESTIGATIVE DERMATOLOGY

Lehden akronyymiJ INVEST DERMATOL

Vuosikerta135

Numero12

Aloitussivu3051

Lopetussivu3059

Sivujen määrä9

ISSN0022-202X

DOIhttps://doi.org/10.1038/jid.2015.320


Tiivistelmä

Extracellular vesicles released from cells regulate many normal and pathological conditions. Little is known about the role of epidermal keratinocyte microvesicles (KC-MVs) in epithelial-stromal interaction that is essential for wound healing. We investigated, therefore, whether MV-like structures are present in human wounds and whether they affect wound healing-associated gene expression in dermal fibroblasts. In human wounds, MV-like vesicles were observed during active epithelial migration and early granulation tissue formation. When KC-MVs derived from keratinocyte-like cells (HaCaT) were added to fibroblast cultures, expression of 21 genes was significantly regulated (P<0.05) out of 80 genes investigated, including matrix metalloproteinase-1 and -3, interleukin-6 and -8, and genes associated with transforming growth factor-beta signaling. Similar changes were observed at the protein level. MVs from normal epidermal keratinocytes showed similar response to HaCaT cells. KC-MVs activated ERK1/2, JNK, Smad, and p38 signaling pathways in fibroblasts with ERK1/2 signaling having the most prominent role in the MV-induced gene expression changes. KC-MVs stimulated fibroblast migration and induced fibroblast-mediated endothelial tube formation but did not affect collagen gel contraction by fibroblasts. The results demonstrate that keratinocyte microvesicles have a strong and a specific regulatory effect on fibroblasts that may modulate several aspects of wound healing.




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