Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice

Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) con...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zdravka Daneva, Matteo Ottolini, Yen Lin Chen, Eliska Klimentova, Maniselvan Kuppusamy, Soham A Shah, Richard D Minshall, Cheikh I Seye, Victor E Laubach, Brant E Isakson, Swapnil K Sonkusare
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	TRP channel Pannexin 1 purinergic signaling Caveolin 1 pulmonary vasculature Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4e52c48d21c241c0a4496dbc4db01f8d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4e52c48d21c241c0a4496dbc4db01f8d
record_format	dspace
spelling	oai:doaj.org-article:4e52c48d21c241c0a4496dbc4db01f8d2021-11-15T07:05:12ZEndothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice10.7554/eLife.677772050-084Xe67777https://doaj.org/article/4e52c48d21c241c0a4496dbc4db01f8d2021-09-01T00:00:00Zhttps://elifesciences.org/articles/67777https://doaj.org/toc/2050-084XPannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) contractility and exogenous ATP activates endothelial TRPV4 channels. We hypothesized that endothelial Panx1–ATP–TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 increased PA contractility and raised PAP in mice. Flow/shear stress increased ATP efflux through endothelial Panx1 in PAs. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Cα (PKCα), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCα, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1–P2Y2R–TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.Zdravka DanevaMatteo OttoliniYen Lin ChenEliska KlimentovaManiselvan KuppusamySoham A ShahRichard D MinshallCheikh I SeyeVictor E LaubachBrant E IsaksonSwapnil K SonkusareeLife Sciences Publications LtdarticleTRP channelPannexin 1purinergic signalingCaveolin 1pulmonary vasculatureMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TRP channel Pannexin 1 purinergic signaling Caveolin 1 pulmonary vasculature Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	TRP channel Pannexin 1 purinergic signaling Caveolin 1 pulmonary vasculature Medicine R Science Q Biology (General) QH301-705.5 Zdravka Daneva Matteo Ottolini Yen Lin Chen Eliska Klimentova Maniselvan Kuppusamy Soham A Shah Richard D Minshall Cheikh I Seye Victor E Laubach Brant E Isakson Swapnil K Sonkusare Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice
description	Pannexin 1 (Panx1), an ATP-efflux pathway, has been linked with inflammation in pulmonary capillaries. However, the physiological roles of endothelial Panx1 in the pulmonary vasculature are unknown. Endothelial transient receptor potential vanilloid 4 (TRPV4) channels lower pulmonary artery (PA) contractility and exogenous ATP activates endothelial TRPV4 channels. We hypothesized that endothelial Panx1–ATP–TRPV4 channel signaling promotes vasodilation and lowers pulmonary arterial pressure (PAP). Endothelial, but not smooth muscle, knockout of Panx1 increased PA contractility and raised PAP in mice. Flow/shear stress increased ATP efflux through endothelial Panx1 in PAs. Panx1-effluxed extracellular ATP signaled through purinergic P2Y2 receptor (P2Y2R) to activate protein kinase Cα (PKCα), which in turn activated endothelial TRPV4 channels. Finally, caveolin-1 provided a signaling scaffold for endothelial Panx1, P2Y2R, PKCα, and TRPV4 channels in PAs, promoting their spatial proximity and enabling signaling interactions. These results indicate that endothelial Panx1–P2Y2R–TRPV4 channel signaling, facilitated by caveolin-1, reduces PA contractility and lowers PAP in mice.
format	article
author	Zdravka Daneva Matteo Ottolini Yen Lin Chen Eliska Klimentova Maniselvan Kuppusamy Soham A Shah Richard D Minshall Cheikh I Seye Victor E Laubach Brant E Isakson Swapnil K Sonkusare
author_facet	Zdravka Daneva Matteo Ottolini Yen Lin Chen Eliska Klimentova Maniselvan Kuppusamy Soham A Shah Richard D Minshall Cheikh I Seye Victor E Laubach Brant E Isakson Swapnil K Sonkusare
author_sort	Zdravka Daneva
title	Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice
title_short	Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice
title_full	Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice
title_fullStr	Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice
title_full_unstemmed	Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice
title_sort	endothelial pannexin 1–trpv4 channel signaling lowers pulmonary arterial pressure in mice
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/4e52c48d21c241c0a4496dbc4db01f8d
work_keys_str_mv	AT zdravkadaneva endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT matteoottolini endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT yenlinchen endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT eliskaklimentova endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT maniselvankuppusamy endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT sohamashah endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT richarddminshall endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT cheikhiseye endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT victorelaubach endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT branteisakson endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice AT swapnilksonkusare endothelialpannexin1trpv4channelsignalinglowerspulmonaryarterialpressureinmice
_version_	1718428494415790080

Endothelial pannexin 1–TRPV4 channel signaling lowers pulmonary arterial pressure in mice

Ejemplares similares