Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells.

Autor:	Adase CA; From the Department of Dermatology, University of California, San Diego, California 92093., Borkowski AW; From the Department of Dermatology, University of California, San Diego, California 92093., Zhang LJ; From the Department of Dermatology, University of California, San Diego, California 92093., Williams MR; From the Department of Dermatology, University of California, San Diego, California 92093., Sato E; From the Department of Dermatology, University of California, San Diego, California 92093., Sanford JA; From the Department of Dermatology, University of California, San Diego, California 92093., Gallo RL; From the Department of Dermatology, University of California, San Diego, California 92093 rgallo@ucsd.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2016 May 27; Vol. 291 (22), pp. 11635-46. Date of Electronic Publication: 2016 Apr 05.
DOI:	10.1074/jbc.M116.725317
Abstrakt:	A critical function for skin is that when damaged it must simultaneously identify the nature of the injury, repair barrier function, and limit the intrusion of pathogenic organisms. These needs are carried out through the detection of damage-associated molecular patterns (DAMPs) and a response that includes secretion of cytokines, chemokines, growth factors, and antimicrobial peptides (AMPs). In this study, we analyzed how non-coding double-stranded RNA (dsRNAs) act as a DAMP in the skin and how the human cathelicidin AMP LL-37 might influence growth factor production in response to this DAMP. dsRNA alone significantly increased the expression of multiple growth factors in keratinocytes, endothelial cells, and fibroblasts. Furthermore, RNA sequencing transcriptome analysis found that multiple growth factors increase when cells are exposed to both LL-37 and dsRNA, a condition that mimics normal wounding. Quantitative PCR and/or ELISA validated that growth factors expressed by keratinocytes in these conditions included, but were not limited to, basic fibroblast growth factor (FGF2), heparin-binding EGF-like growth factor (HBEGF), vascular endothelial growth factor C (VEGFC), betacellulin (BTC), EGF, epiregulin (EREG), and other members of the transforming growth factor β superfamily. These results identify a novel role for DAMPs and AMPs in the stimulation of repair and highlight the complex interactions involved in the wound environment. (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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