DNA methylation and gene expression profiling reveal MFAP5 as a regulatory driver of extracellular matrix remodeling in varicose vein disease.

Autor:	Smetanina MA; Laboratory of Pharmacogenomics, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.; Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk 630090, Russia., Kel AE; Laboratory of Pharmacogenomics, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.; Department of Research & Development, geneXplain GmbH, Wolfenbüttel D-38302, Germany., Sevost'ianova KS; Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk 630090, Russia.; Center of New Medical Technologies, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia., Maiborodin IV; Stem Cell Laboratory, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia., Shevela AI; Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk 630090, Russia.; Center of New Medical Technologies, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia., Zolotukhin IA; Laboratory of Pharmacogenomics, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.; Chair of Faculty Surgery of the Medical Department, Pirogov Russian National Research Medical University, Moscow 117997, Russia., Stegmaier P; Department of Research & Development, geneXplain GmbH, Wolfenbüttel D-38302, Germany., Filipenko ML; Laboratory of Pharmacogenomics, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia.; Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk 630090, Russia.
Jazyk:	angličtina
Zdroj:	Epigenomics [Epigenomics] 2018 Aug; Vol. 10 (8), pp. 1103-1119. Date of Electronic Publication: 2018 Aug 02.
DOI:	10.2217/epi-2018-0001
Abstrakt:	Aim: To integrate transcriptomic and DNA-methylomic measurements on varicose versus normal veins using a systems biological analysis to shed light on the interplay between genetic and epigenetic factors. Materials & Methods: Differential expression and methylation were measured using microarrays, supported by real-time quantitative PCR and immunohistochemistry confirmation for relevant gene products. A systems biological 'upstream analysis' was further applied. Results: We identified several potential key players contributing to extracellular matrix remodeling in varicose veins. Specifically, our analysis suggests MFAP5 acting as a master regulator, upstream of integrins, of the cellular network affecting the varicose vein condition. Possible mechanism and pathogenic model were outlined. Conclusion: A coherent model proposed incorporates the relevant signaling networks and will hopefully aid further studies on varicose vein pathogenesis.
Databáze:	MEDLINE
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