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Hydrostatic pressure promotes endothelial tube formation through aquaporin 1 and Ras-ERK signaling.

Communications biology (2020-04-04)
Daisuke Yoshino, Kenichi Funamoto, Kakeru Sato, Kenry, Masaaki Sato, Chwee Teck Lim
ABSTRACT

Vascular tubulogenesis is tightly linked with physiological and pathological events in the living body. Endothelial cells (ECs), which are constantly exposed to hemodynamic forces, play a key role in tubulogenesis. Hydrostatic pressure in particular has been shown to elicit biophysical and biochemical responses leading to EC-mediated tubulogenesis. However, the relationship between tubulogenesis and hydrostatic pressure remains to be elucidated. Here, we propose a specific mechanism through which hydrostatic pressure promotes tubulogenesis. We show that pressure exposure transiently activates the Ras/extracellular signal-regulated kinase (ERK) pathway in ECs, inducing endothelial tubulogenic responses. Water efflux through aquaporin 1 and activation of protein kinase C via specific G protein-coupled receptors are essential to the pressure-induced transient activation of the Ras/ERK pathway. Our approach could provide a basis for elucidating the mechanopathology of tubulogenesis-related diseases and the development of mechanotherapies for improving human health.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Protease Inhibitor Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
Gelatin from bovine skin, Type B, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Medium 199, With Hanks′ salts and L-glutamine, without sodium bicarbonate, powder, suitable for cell culture