Cytoskeletal Remodeling Mimics Endothelial Response to Microgravity.

Laura Locatelli,Jeanette A M Maier

doi:10.3389/fcell.2021.733573

Abstract

Mechanical cues contribute to the maintenance of a healthy endothelium, which is essential for vascular integrity. Indeed endothelial cells are mechanosensors that integrate the forces in the form of biochemical signals. The cytoskeleton is fundamental in sensing mechanical stimuli and activating specific signaling pathways. Because the cytoskeleton is very rapidly remodeled in endothelial cells exposed to microgravity, we investigated whether the disruption of actin polymerization by cytochalasin D in 1g condition triggers and orchestrates responses similar to those occurring in micro- and macro-vascular endothelial cells upon gravitational unloading. We focused our attention on the effect of simulated microgravity on stress proteins and transient receptor potential melastatin 7 (TRPM7), a cation channel that acts as a mechanosensor and modulates endothelial cell proliferation and stress response. Simulated microgravity downregulates TRPM7 in both cell types. However, 24 h of treatment with cytochalasin D decreases the amounts of TRPM7 only in macrovascular endothelial cells, suggesting that the regulation and the role of TRPM7 in microvascular cells are more complex than expected. The 24 h culture in the presence of cytochalasin D mimics the effect of simulated microgravity in modulating stress response in micro- and macro-vascular endothelial cells. We conclude that cytoskeletal disruption might mediate some effects of microgravity in endothelial cells.

Highlights

At the interface between the blood and the tissues, vascular endothelial cells (EC) are constantly exposed to a myriad of stimuli which finely shape their phenotype and tune their function
Because the cytoskeleton is very rapidly remodeled in endothelial cells exposed to microgravity, we investigated whether the disruption of actin polymerization by cytochalasin D in 1g condition triggers and orchestrates responses similar to those occurring in microand macro-vascular endothelial cells upon gravitational unloading
We focused our attention on the effect of simulated microgravity on stress proteins and transient receptor potential melastatin 7 (TRPM7), a cation channel that acts as a mechanosensor and modulates endothelial cell proliferation and stress response

Summary

Introduction

At the interface between the blood and the tissues, vascular endothelial cells (EC) are constantly exposed to a myriad of stimuli which finely shape their phenotype and tune their function. Hormones, growth factors, cytokines, a high concentration of oxygen, and mechanical stresses induce a series of active adaptive processes to maintain cell homeostasis (Michiels, 2003; Schober, 2008; Deng et al, 2014; Zhang and Dong, 2014; Zhang and Li, 2017; Marsboom and Rehman, 2018). This is crucial because endothelial cells are in charge of the integrity of the whole vascular tree, which means, among others, to grant adequate perfusion and nourishment to all the tissues (Davies, 2009). EC in microgravity, like all the eukaryotic cells studied until now, remodel their cytoskeleton (Carlsson et al, 2003; Versari et al, 2007; Kapitonova et al, 2012; Janmaleki et al, 2016), and this might be one of the mechanisms impacting on alterations of cell behavior (Carlsson et al, 2003; Cotrupi et al, 2005; Versari et al, 2007, 2013; Kapitonova et al, 2012; Grenon et al, 2013; Maier et al, 2015)

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Results

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