Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension

Chen, Jiyuan; Miao, Jinrui; Zhou, Dansha; Liao, Jing; Wang, Ziyi; Lin, Ziying; Zhang, Chenting; Luo, Xiaoning; Li, Yang; Li, Xiang; Liu, Shiyun; Xing, Yue; Zhang, Zizhou; Zhao, Manjia; Parmisano, Sophia; Chen, Yuqin; Yuan, Jason X.‐J.; Yang, Kai; Sun, Dejun; Wang, Jian

doi:10.1016/j.thromres.2022.08.006

Cited by 14 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study shows that RELA (i.e., p65) overexpression in human pulmonary artery endothelial cells induces upregulation of PIEZO1; meanwhile, p65 silencing downregulates PIEZO1 [34]. In this study, we added detailed evidence concerning the regulatory mechanisms of PIEZO1 by the pro-inflammatory and prooxidant transcription factor NF-κB.…”

Section: Discussionmentioning

confidence: 92%

Transcriptional Profiling of Human Endothelial Cells Unveils PIEZO1 and Mechanosensitive Gene Regulation by Prooxidant and Inflammatory Inputs

Arenas,

Valenzuela,

Peñaloza

et al. 2023

Antioxidants

View full text Add to dashboard Cite

PIEZO1 is a mechanosensitive cation channel implicated in shear stress-mediated endothelial-dependent vasorelaxation. Since altered shear stress patterns induce a pro-inflammatory endothelial environment, we analyzed transcriptional profiles of human endothelial cells to determine the effect of altered shear stress patterns and subsequent prooxidant and inflammatory conditions on PIEZO1 and mechanosensitive-related genes (MRG). In silico analyses were validated in vitro by assessing PIEZO1 transcript levels in both the umbilical artery (HUAEC) and vein (HUVEC) endothelium. Transcriptional profiling showed that PIEZO1 and some MRG associated with the inflammatory response were upregulated in response to high (15 dyn/cm2) and extremely high shear stress (30 dyn/cm2) in HUVEC. Changes in PIEZO1 and inflammatory MRG were paralleled by p65 but not KLF or YAP1 transcription factors. Similarly, PIEZO1 transcript levels were upregulated by TNF-alpha (TNF-α) in diverse endothelial cell types, and pre-treatment with agents that prevent p65 translocation to the nucleus abolished PIEZO1 induction. ChIP-seq analysis revealed that p65 bonded to the PIEZO1 promoter region, an effect increased by the stimulation with TNF-α. Altogether this data showed that NF-kappa B activation via p65 signaling regulates PIEZO1 expression, providing a new molecular link for prooxidant and inflammatory responses and mechanosensitive pathways in the endothelium.

show abstract

Section: Discussionmentioning

confidence: 92%

Transcriptional Profiling of Human Endothelial Cells Unveils PIEZO1 and Mechanosensitive Gene Regulation by Prooxidant and Inflammatory Inputs

Arenas,

Valenzuela,

Peñaloza

et al. 2023

Antioxidants

View full text Add to dashboard Cite

show abstract

“…Upregulation of the channel can happen through different stimuli such as shear stress; increased stiffness of the extracellular environment; and signals coming from injury, inflammatory cytokines or other metabolites. Shear stress is implicated in Piezo1 upregulation in various cell types such as in endothelial and vascular cells in the context of pulmonary hypertension [ 34 , 35 ], in endothelial cells via adrenomedullin [ 36 ] and in megakaryocytes (MKs) and platelets with the activation of integrins [ 37 ]. Stiffness sensation by Piezo1 was found to be associated with upregulation of the expression of the channel in MKs, as proven by culturing these cells in a 3D culture medium of different stiffness and by its enhanced MK expression in the case of primary myelofibrosis (PMF), a disease characterized by bone marrow fibrosis and augmented stiffness of the extracellular matrix (ECM) [ 38 ].…”

Section: Overview Of Piezo1 Propertiesmentioning

confidence: 99%

Piezo1 and Its Function in Different Blood Cell Lineages

Karkempetzaki,

Ravid

2024

Cells

View full text Add to dashboard Cite

Mechanosensation is a fundamental function through which cells sense mechanical stimuli by initiating intracellular ion currents. Ion channels play a pivotal role in this process by orchestrating a cascade of events leading to the activation of downstream signaling pathways in response to particular stimuli. Piezo1 is a cation channel that reacts with Ca2+ influx in response to pressure sensation evoked by tension on the cell lipid membrane, originating from cell–cell, cell–matrix, or hydrostatic pressure forces, such as laminar flow and shear stress. The application of such forces takes place in normal physiological processes of the cell, but also in the context of different diseases, where microenvironment stiffness or excessive/irregular hydrostatic pressure dysregulates the normal expression and/or activation of Piezo1. Since Piezo1 is expressed in several blood cell lineages and mutations of the channel have been associated with blood cell disorders, studies have focused on its role in the development and function of blood cells. Here, we review the function of Piezo1 in different blood cell lineages and related diseases, with a focus on megakaryocytes and platelets.

show abstract

“…185 PIEZO1 was also upregulated in arterial smooth muscle cells in patients with idiopathic pulmonary hypertension. 76,186,187 It remains to be established whether alteration in PIEZO1 expression is the cause or consequence of the cardiovascular diseases.…”

Section: Genetic Linkage To Human Cardiovascular Diseasesmentioning

confidence: 99%

PIEZO Ion Channels in Cardiovascular Functions and Diseases

Coste,

Delmas

2024

Circulation Research

View full text Add to dashboard Cite

The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after mechanosensitive excitatory channels involved in touch and proprioception in mammals. However, more and more pieces of evidence point to the importance of PIEZO channels in cardiovascular activities and disease development. PIEZO channel-related cardiac functions include transducing hemodynamic forces in endothelial and vascular cells, red blood cell homeostasis, platelet aggregation, and arterial blood pressure regulation, among others. PIEZO channels contribute to pathological conditions including cardiac hypertrophy and pulmonary hypertension and congenital syndromes such as generalized lymphatic dysplasia and xerocytosis. In this review, we highlight recent advances in understanding the role of PIEZO channels in cardiovascular functions and diseases. Achievements in this quickly expanding field should open a new road for efficient control of PIEZO-related diseases in cardiovascular functions.

show abstract

Upregulation of mechanosensitive channel Piezo1 involved in high shear stress-induced pulmonary hypertension

Cited by 14 publications

References 29 publications

Transcriptional Profiling of Human Endothelial Cells Unveils PIEZO1 and Mechanosensitive Gene Regulation by Prooxidant and Inflammatory Inputs

Transcriptional Profiling of Human Endothelial Cells Unveils PIEZO1 and Mechanosensitive Gene Regulation by Prooxidant and Inflammatory Inputs

Piezo1 and Its Function in Different Blood Cell Lineages

PIEZO Ion Channels in Cardiovascular Functions and Diseases

Contact Info

Product

Resources

About