Table 2 Conditional deletion of Piezo1 in experimental mice

From: Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues

Tissue type

Cre

Phenotype

Mechanism

Global deletion

63

Embryos died at E9.5 lacking modeling of vasculature

Impaired endothelial cell alignment in response to shear stress; failing to remodel arteries

Endothelial cells

Cadherin5-CreERT2181

Inhibited Ca2+ influx induced by Yoda1; more sensitive to α-adrenergic agonists

 
 

Cadherin5-CreERT2137

Impaired physical performance and lower body weight after sustained activity

Piezo1 transduced fluid flow signal to constriction of mesenteric arteries, which are responsible for total peripheral resistance

 

iEC-Cre132

Increased lung vascular permeability by high-volume mechanical ventilation

Piezo1 targeted calcium-dependent cysteine protease calpain to maintain homeostasis of the endothelial barrier

 

iEC-Cre133

Increased lung microvessel pressure; impaired regulation of lung endothelial barrier

Piezo1 regulated lung vascular permeability by targeting endothelial VE-cadherin

 

Tie2-Cre or Lyve1-Cre134

Reduced amount of lymphatic valves

 
 

Tie2-CreERT2138

Upregulated arterial blood pressure

Failed to produce NO or vasodilate because of insensitivity to flow stimulation

Adult endothelial cells

SCL-CreERT136

Impaired angiogenesis; inhibited endothelial sprouting and lumen formation after subjected to wall shear stress

Piezo1 increased intracellular Ca2+ and activated MT1-MMP pathway

Lymphatic endothelial cells

Prox1-CreERT2135

Inhibited formation and maintenance of lymphatic valves and lymphatic vessels

Piezo1 transduced the signal of OSS to control lymphatic valves and lymphatic vessels

Smooth muscle cells

sm22-Cre14

Reduced activity of ion channels in caudal artery myocytes induced by stretch; reduced arterial diameter, wall thickness, and cross-sectional area treated with Angiotensin II

Piezo1 sensed flow and pressure to regulate structural remodeling of arteries

Adipocytes

Adiponectin-Cre141

Increased insulin resistance; decreased pgWAT weight and increased pro-inflammatory and lipolysis genes after HFD fed; hepatic steatosis with increased fatty acid synthesis genes

Piezo1 participated in TLR4-mediated inflammation

 

Adiponectin-CreERT2140

Impaired adipocyte differentiation, causing inflammation and insulin insensitivity

Piezo1 promoted the secretion of adipogenic FGF1 to facilitate adipocyte precursor differentiation

Myeloid cells

LysM-Cre143

Ameliorated pulmonary inflammation

Piezo1 exhibited proinflammatory effects by activating AP-1c and EDN1 and stabilizing HIF1α

Acinar cells

Ptf1a-CreER142

Ameliorated pancreatitis, including reduced edema, neutrophil infiltration, hemorrhage, and tissue necrosis

Piezo1 activated cytoplasmic calcium signals that are toxic to pancreatic acinar cells, resulting in cellular necrosis and pancreatitis

Nodose and petrosal sensory ganglia neurons

Phox2b-Cre Piezo1/2 dKO156

Attenuated baroreflex and activity of aortic depressor nerve

 

DRG neurons

shRNA KD159

Inhibited Ca2+ influx induced by Yoda1

The mechanism is still unclear whether targeting Ca2+ -induced phospholipase C δ, β, or other signaling pathways

  1. E embryonic, VE vascular endothelial, NO nitric oxide, MT1 membrane-type 1, MMP matrix metalloproteinase, OSS oscillating shear stress, pgWAT perigonadal white adipose tissue, HFD high fat diet, TLR4 Toll-like receptor 4, FGF1 fibroblast growth factor 1, AP-1 activator protein-1, EDN1 endothelin-1, HIF1α hypoxia-inducible factor-1α, DRG dorsal root ganglion