Clonal hematopoiesis with JAK2V617F promotes pulmonary hypertension with ALK1 upregulation in lung neutrophils.

Activin Receptors, Type II / genetics Animals Bone Marrow Cells / cytology Cell Line, Tumor Clonal Hematopoiesis / genetics Humans Hypertension, Pulmonary / genetics Hypoxia / metabolism Janus Kinase 2 / genetics Lung / immunology Mice Mice, Transgenic Mutation Myeloproliferative Disorders / genetics Neutrophil Infiltration Neutrophils / immunology Phosphorylation Prevalence STAT3 Transcription Factor / metabolism Signal Transduction Smad Proteins / metabolism Up-Regulation Vascular Remodeling

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 10 2021
Historique:
received: 11 05 2020
accepted: 05 10 2021
entrez: 27 10 2021
pubmed: 28 10 2021
medline: 1 12 2021
Statut: epublish

Résumé

Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by pulmonary arterial remodeling. Clonal somatic mutations including JAK2V617F, the most frequent driver mutation among myeloproliferative neoplasms, have recently been identified in healthy individuals without hematological disorders. Here, we reveal that clonal hematopoiesis with JAK2V617F exacerbates PH and pulmonary arterial remodeling in mice. JAK2V617F-expressing neutrophils specifically accumulate in pulmonary arterial regions, accompanied by increases in neutrophil-derived elastase activity and chemokines in chronic hypoxia-exposed JAK2V617F transgenic (JAK2

Identifiants

DOI: 10.1038/s41467-021-26435-0 PMID: 34702814 PMC: PMC8548396
pubmed: 34702814
doi: 10.1038/s41467-021-26435-0
pii: 10.1038/s41467-021-26435-0
pmc: PMC8548396
doi:

Substances chimiques

STAT3 Transcription Factor 0
Smad Proteins 0
JAK2 protein, human EC 2.7.10.2
Janus Kinase 2 EC 2.7.10.2
Activin Receptors, Type II EC 2.7.11.30

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6177

Informations de copyright

© 2021. The Author(s).

Références

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Auteurs

Yusuke Kimishima (Y)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.
ORCID: 0000-0003-4470-2365

Tomofumi Misaka (T)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan. misaka83@fmu.ac.jp.
Department of Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan. misaka83@fmu.ac.jp.
ORCID: 0000-0003-4795-9334

Tetsuro Yokokawa (T)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.
Department of Pulmonary Hypertension, Fukushima Medical University, Fukushima, Japan.
ORCID: 0000-0001-8197-3274

Kento Wada (K)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Koki Ueda (K)

Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan.
ORCID: 0000-0002-6964-7035

Koichi Sugimoto (K)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.
Department of Pulmonary Hypertension, Fukushima Medical University, Fukushima, Japan.

Keiji Minakawa (K)

Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan.

Kazuhiko Nakazato (K)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Takafumi Ishida (T)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

Motohiko Oshima (M)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Shuhei Koide (S)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

Kotaro Shide (K)

Department of Gastroenterology and Hematology, University of Miyazaki, Miyazaki, Japan.

Kazuya Shimoda (K)

Department of Gastroenterology and Hematology, University of Miyazaki, Miyazaki, Japan.
ORCID: 0000-0002-2555-8188

Atsushi Iwama (A)

Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
ORCID: 0000-0001-9410-8992

Kazuhiko Ikeda (K)

Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University, Fukushima, Japan. kazu-ike@fmu.ac.jp.
ORCID: 0000-0002-5269-269X

Yasuchika Takeishi (Y)

Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs TGF-bêta › Récepteur activine › Récepteur activine, type 2 › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Hématopoïèse clonale › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Hypertension artérielle › Hypertension pulmonaire › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Signes et symptômes respiratoires › Hypoxie › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Kinase Janus-2 › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Appareil respiratoire › Poumon › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Maladies de la moelle osseuse › Syndromes myéloprolifératifs › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Phénomènes du système immunitaire › Infiltration par les neutrophiles › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Granulocytes neutrophiles › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Métabolisme › Phosphorylation › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Morbidité › Prévalence › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-3 › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines Smad › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Clonal hematopoiesis with JAK2V617F promotes...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Remodelage vasculaire › Clonal hematopoiesis with JAK2V617F promotes...