Mariya A Smetanina1,2, Alexander E Kel1,3, Ksenia S Sevost'ianova2,4, Igor V Maiborodin5, Andrey I Shevela2,4, Igor A Zolotukhin1,6, Philip Stegmaier3, Maxim L Filipenko1,2. 1. Laboratory of Pharmacogenomics, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia. 2. Department of Fundamental Medicine, Novosibirsk State University, Novosibirsk 630090, Russia. 3. Department of Research & Development, geneXplain GmbH, Wolfenbüttel D-38302, Germany. 4. Center of New Medical Technologies, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia. 5. Stem Cell Laboratory, Institute of Chemical Biology & Fundamental Medicine, Novosibirsk 630090, Russia. 6. Chair of Faculty Surgery of the Medical Department, Pirogov Russian National Research Medical University, Moscow 117997, Russia.
Abstract
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.
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.
Entities:
Keywords:
DNA methylation; MFAP5; extracellular matrix; gene expression; systems biological analysis; varicose vein(s); vascular remodeling
Authors: V A Korolenya; K A Gavrilov; K S Sevost'ianova; A I Shevela; M L Filipenko; M A Smetanina Journal: Bull Exp Biol Med Date: 2022-07-19 Impact factor: 0.737