Cargando…
PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension
Bone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH. To identify whether PTPs...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857213/ https://www.ncbi.nlm.nih.gov/pubmed/36672250 http://dx.doi.org/10.3390/cells12020316 |
_version_ | 1784873816093097984 |
---|---|
author | Ali, Md Khadem Tian, Xuefei Zhao, Lan Schimmel, Katharina Rhodes, Christopher J. Wilkins, Martin R. Nicolls, Mark R. Spiekerkoetter, Edda F. |
author_facet | Ali, Md Khadem Tian, Xuefei Zhao, Lan Schimmel, Katharina Rhodes, Christopher J. Wilkins, Martin R. Nicolls, Mark R. Spiekerkoetter, Edda F. |
author_sort | Ali, Md Khadem |
collection | PubMed |
description | Bone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH. To identify whether PTPs modify BMPR2 signaling, we used a siRNA-mediated high-throughput screening of 22,124 murine genes in mouse myoblastoma reporter cells using ID1 expression as readout for BMPR2 signaling. We further experimentally validated the top hit, PTPN1 (PTP1B), in healthy human pulmonary arterial endothelial cells (PAECs) either silenced by siRNA or exposed to hypoxia and confirmed its relevance to PAH by measuring PTPN1 levels in blood and PAECs collected from PAH patients. We identified PTPN1 as a novel regulator of BMPR2 signaling in PAECs, which is downregulated in the blood of PAH patients, and documented that downregulation of PTPN1 is linked to endothelial dysfunction in PAECs. These findings point to a potential involvement for PTPN1 in PAH and will aid in our understanding of the molecular mechanisms involved in the disease. |
format | Online Article Text |
id | pubmed-9857213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98572132023-01-21 PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension Ali, Md Khadem Tian, Xuefei Zhao, Lan Schimmel, Katharina Rhodes, Christopher J. Wilkins, Martin R. Nicolls, Mark R. Spiekerkoetter, Edda F. Cells Article Bone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH. To identify whether PTPs modify BMPR2 signaling, we used a siRNA-mediated high-throughput screening of 22,124 murine genes in mouse myoblastoma reporter cells using ID1 expression as readout for BMPR2 signaling. We further experimentally validated the top hit, PTPN1 (PTP1B), in healthy human pulmonary arterial endothelial cells (PAECs) either silenced by siRNA or exposed to hypoxia and confirmed its relevance to PAH by measuring PTPN1 levels in blood and PAECs collected from PAH patients. We identified PTPN1 as a novel regulator of BMPR2 signaling in PAECs, which is downregulated in the blood of PAH patients, and documented that downregulation of PTPN1 is linked to endothelial dysfunction in PAECs. These findings point to a potential involvement for PTPN1 in PAH and will aid in our understanding of the molecular mechanisms involved in the disease. MDPI 2023-01-14 /pmc/articles/PMC9857213/ /pubmed/36672250 http://dx.doi.org/10.3390/cells12020316 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ali, Md Khadem Tian, Xuefei Zhao, Lan Schimmel, Katharina Rhodes, Christopher J. Wilkins, Martin R. Nicolls, Mark R. Spiekerkoetter, Edda F. PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension |
title | PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension |
title_full | PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension |
title_fullStr | PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension |
title_full_unstemmed | PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension |
title_short | PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension |
title_sort | ptpn1 deficiency modulates bmpr2 signaling and induces endothelial dysfunction in pulmonary arterial hypertension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857213/ https://www.ncbi.nlm.nih.gov/pubmed/36672250 http://dx.doi.org/10.3390/cells12020316 |
work_keys_str_mv | AT alimdkhadem ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT tianxuefei ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT zhaolan ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT schimmelkatharina ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT rhodeschristopherj ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT wilkinsmartinr ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT nicollsmarkr ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension AT spiekerkoettereddaf ptpn1deficiencymodulatesbmpr2signalingandinducesendothelialdysfunctioninpulmonaryarterialhypertension |