Piezo1, a mechanically activated ion channel, is required for vascular development in mice

Abstract

Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development.

Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells

“…The Piezo1 protein was discovered recently and was shown to be the poreforming subunit of a nonspecific cation channel that is intrinsically gated by membrane tension (31,32). Recent studies demonstrate a role for Piezo1 in regulating erythrocyte volume (43), epithelial crowding and homeostasis (36), cell migration (44), and detection of blood flow (33,34). Our results suggest a role for Piezo1 in detecting matrix elasticity and determining lineage choice.…”

“…Of these, Piezo1 was expressed at much greater levels than the other channels. The Piezo channels recently were shown to mediate physiologically relevant mechanically activated and nonspecific cationic currents in mammals (30)(31)(32)(33)(34). Like the endogenous hNSPC SAC, Piezo1 is inactivated by persisting mechanical stimuli (31) and is sensitive to GsMTx-4 (35).…”

“…Piezo1 has been implicated in cellular processes in which cells respond to an external mechanical force, e.g., a stretch stimulus, osmotic pressure, or shear stress (31,33,34,(36)(37)(38). We asked whether cell-generated forces, such as traction forces, also can activate Piezo1.…”

TACAN is an essential component of the mechanosensitive ion channel responsible for pain sensing

“…Much like the Piezo family of MSC, which was found to be involved in touch (Ranade et al, 2014b), proprioception (Woo et al, 2015), lung inflation (Nonomura et al, 2017), vascular development (Ranade et al, 2014a), and red blood cell volume regulation (Cahalan et al, 2015;Ma et al, 2018), TACAN is expressed in many tissues and likely to play important roles in several mechanotransduction processes. TACAN also has a homolog in mammalian cells, TMEM120B, but its heterologous expression did not increase mechanically-evoked currents ( Figure S6).…”

MiR-103a targeting Piezo1 is involved in acute myocardial infarction through regulating endothelium function

“…Piezo1 protein has been identified as an essential component of mechanically activated channels and induces cationic non-selective mechanically activated currents [24,25]. The role of Piezo1 gene has been linked recently to the vascular biology [11].…”