Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation

Jiyuan Chen, Marisela Rodriguez, Jinrui Miao, Jing Liao, Pritesh P. Jain, Manjia Zhao, Tengteng Zhao, Aleksandra Babicheva, Ziyi Wang, Sophia Parmisano, Ryan Powers, Moreen Matti, Cole Paquin, Zahra Soroureddin, John Y.J. Shyy, Patricia A. Thistlethwaite, Ayako Makino, Jian Wang, Jason X.J. Yuan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Concentric pulmonary vascular wall thickening due partially to increased pulmonary artery (PA) smooth muscle cell (PASMC) proliferation contributes to elevating pulmonary vascular resistance (PVR) in patients with pulmonary hypertension (PH). Although pulmonary vasoconstriction may be an early contributor to increasing PVR, the transition of contractile PASMCs to proliferative PASMCs may play an important role in the development and progression of pulmonary vascular remodeling in PH. A rise in cytosolic Ca2 þ concentration ([Ca2 þ ]cyt) is a trigger for PASMC contraction and proliferation. Here, we report that upregulation of Piezo1, a mechanosensitive cation channel, is involved in the contractile-to-proliferative phenotypic transition of PASMCs and potential development of pulmonary vascular remodeling. By comparing freshly isolated PA (contractile PASMCs) and primary cultured PASMCs (from the same rat) in a growth medium (proliferative PASMCs), we found that Piezo1, Notch2/3, and CaSR protein levels were significantly higher in proliferative PASMCs than in contractile PASMCs. Upregulated Piezo1 was associated with an increase in expression of PCNA, a marker for cell proliferation, whereas downregulation (with siRNA) or inhibition (with GsMTx4) of Piezo1 attenuated PASMC proliferation. Furthermore, Piezo1 in the remodeled PA from rats with experimental PH was upregulated compared with PA from control rats. These data indicate that PASMC contractile-to-proliferative phenotypic transition is associated with the transition or adaptation of membrane channels and receptors. Upregulated Piezo1 may play a critical role in PASMC phenotypic transition and PASMC proliferation. Upregulation of Piezo1 in proliferative PASMCs may likely be required to provide sufficient Ca2 þ to assure nuclear/cell division and PASMC proliferation, contributing to the development and progression of pulmonary vascular remodeling in PH.

Original languageEnglish (US)
Pages (from-to)L737-L760
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume322
Issue number5
DOIs
StatePublished - 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (R35 HL135807 and R01HL146764).

Publisher Copyright:
Copyright © 2022 the American Physiological Society.

Keywords

  • mechanosensitive channel
  • phenotypic transition
  • Piezo1
  • pulmonary hypertension
  • smooth muscle cell

PubMed: MeSH publication types

  • Journal Article

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