Cells (Basel, Switzerland), 2023-01, Vol.12 (2), p.316
2023
Details
- Autor(en) / Beteiligte
- Titel
- PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension
- Ist Teil von
- Cells (Basel, Switzerland), 2023-01, Vol.12 (2), p.316
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2023
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2073-4409eISSN: 2073-4409DOI: 10.3390/cells12020316Titel-ID: cdi_doaj_primary_oai_doaj_org_article_39d052282cc64d45b9ac50bfe066e383
- Format
- –
- Schlagworte
- Angiogenesis, Animals, Apoptosis, BMPR2 signaling, Bone morphogenetic protein receptor type II, Bone Morphogenetic Protein Receptors, Type II - genetics, Bone Morphogenetic Protein Receptors, Type II - metabolism, Carotid arteries, Cells, Endothelial cells, Endothelial Cells - metabolism, endothelial dysfunction, Gene expression, High-throughput screening, Humans, Hypertension, Hypertension, Pulmonary - metabolism, Hypoxia, Id1 protein, Kinases, Mice, Molecular modelling, Mutation, Pathogenesis, Phosphatase, Protein Tyrosine Phosphatase, Non-Receptor Type 1 - genetics, Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism, Proteins, PTPN1, Pulmonary Arterial Hypertension - metabolism, Pulmonary arteries, Pulmonary Artery - metabolism, Pulmonary hypertension, RNA, Small Interfering - metabolism, Signal transduction, siRNA, Smooth muscle, Tyrosine, Vascular Diseases - metabolism, Veins & arteries