A Mathematical Model Linking Ca2+-Dependent Signaling Pathway and Gene Expression Regulation in Human Skeletal Muscle
Akberdin I.R.1,2,3, Vertyshev A.Yu.4, Pintus S.S.1,5, Popov D.V.6, Kolpakov F.A.1,5
1BIOSOFT.RU, LLC, Novosibirsk, Russian Federation
2Federal Research Center Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia
3Novosibirsk State University, Novosibirsk, Russian Federation
4CJSC "Sites-Tsentr", Moscow, Russian Federation
5Institute of Computational Technologies SB RAS, Novosibirsk, Russian Federation
6Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow, Russia
Abstract. The physiological adaptation to aerobic endurance exercises is provided by activation of signaling pathways in skeletal muscle cells. Training-induced activation of specific signaling pathways results in significant transcriptional responses. Despite the ongoing endeavours to experimentally investigate regulatory mechanisms and signal transduction pathways involved in the contraction-induced adaptation, quantitative contribution of certain signal molecules in expression regulation of genes responsible for intracellular response has not been studied comprehensively yet. The paper presents novel developed model linking Ca2+-dependent signaling pathway and downstream transcription regulation of early and late response genes in human skeletal muscle during exercise. Numerical analysis of the model enabled to reveal crucial steps in this signal transduction pathway for the adaptation and demonstrated the necessity of consideration of additional transcription factors regulating transcription of late response genes in order to adequately reproduce gene expression data that were taken in human vastus lateralis muscle during and after acute cycling exercise.
Key words: mathematical model, skeletal muscle, physical exercise, Ca2+-dependent signaling pathway, transcriptome, RNA sequencing, regulation of expression, BioUML.