Stress-induced ECM alteration modulates cellular microRNAs that feedback to readjust the extracellular environment and cell behavior

Abstract

The extracellular environment is a complex entity comprising of the extracellular matrix (ECM) and regulatory molecules. It is highly dynamic and under cell-extrinsic stress, transmits the stressed organism's state to each individual ECM-connected cell. microRNAs (miRNAs) are regulatory molecules involved in virtually all the processes in the cell, especially under stress. In this review, we analyse how miRNA expression is regulated downstream of various signal transduction pathways induced by changes in the extracellular environment. In particular, we focus on the muscular dystrophy-associated cell adhesion molecule dystroglycan capable of signal transduction. Then we show how exactly the same miRNAs feedback to regulate the extracellular environment. The ultimate goal of this bi-directional signal transduction process is to change cell behavior under cell-extrinsic stress in order to respond to it accordingly. Each individual organism in its lifetime has to cope with multiple kinds of stress that occur when body's homeostasis is shifted from its optimal state. Development, puberty, changing environmental conditions, injuries, diseases, and aging - all influence the organism as a whole no matter which cell or system was the first to encounter the stressor. Organism's systemic reaction to stress is achieved because cells are not isolated from each other. Rather, they communicate through direct cell-cell contacts or via the extracellular matrix (ECM). In this review, in the beginning we introduce the ECM and the cell-extrinsic stress-induced signaling molecules. We define the extracellular environment, focusing on how it can encode for stress signals. We then discuss how a cell can read the encoded signals, focusing on cell adhesion molecule dystroglycan (Dg) capable of outside-in signal transduction. In the last two parts of the review, we show how a cell can change levels of intracellular microRNAs (miRNAs) in response to outside stress signals, and how these miRNAs can then modulate the cell behavior by targeting components of the extracellular environment. © 2013 Edeleva and Shcherbata.