| Mesodermal Pten inactivation leads to alveolar capillary dysplasia- like phenotype. | |
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MedLine Citation:
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PMID: 23023706 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alveolar capillary dysplasia (ACD) is a congenital, lethal disorder of the pulmonary vasculature. Phosphatase and tensin homologue deleted from chromosome 10 (Pten) encodes a lipid phosphatase controlling key cellular functions, including stem/progenitor cell proliferation and differentiation; however, the role of PTEN in mesodermal lung cell lineage formation remains unexamined. To determine the role of mesodermal PTEN in the ontogeny of various mesenchymal cell lineages during lung development, we specifically deleted Pten in early embryonic lung mesenchyme in mice. Pups lacking Pten died at birth, with evidence of failure in blood oxygenation. Analysis at the cellular level showed defects in angioblast differentiation to endothelial cells and an accompanying accumulation of the angioblast cell population that was associated with disorganized capillary beds. We also found decreased expression of Forkhead box protein F1 (Foxf1), a gene associated with the ACD human phenotype. Analysis of human samples for ACD revealed a significant decrease in PTEN and increased activated protein kinase B (AKT). These studies demonstrate that mesodermal PTEN has a key role in controlling the amplification of angioblasts as well as their differentiation into endothelial cells, thereby directing the establishment of a functional gas exchange interface. Additionally, these mice could serve as a murine model of ACD. |
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Authors:
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Caterina Tiozzo; Gianni Carraro; Denise Al Alam; Sheryl Baptista; Soula Danopoulos; Aimin Li; Maria Lavarreda-Pearce; Changgong Li; Stijn De Langhe; Belinda Chan; Zea Borok; Saverio Bellusci; Parviz Minoo |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 122 ISSN: 1558-8238 ISO Abbreviation: J. Clin. Invest. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-12-26 Completed Date: 2013-01-15 Revised Date: 2013-02-20 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 3862-72 Citation Subset: AIM; IM |
Affiliation:
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Department of Pediatrics, Division of Newborn Medicine, University of Southern California, Children's Hospital, Los Angeles, California, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation* Cell Lineage Endothelial Cells / enzymology*, pathology Enzyme Activation Forkhead Transcription Factors / genetics, metabolism Humans Lung / embryology*, enzymology, pathology Mesoderm / embryology*, enzymology, pathology Mice Mice, Knockout PTEN Phosphohydrolase / genetics, metabolism* Persistent Fetal Circulation Syndrome / embryology*, enzymology, genetics, pathology Phenotype Proto-Oncogene Proteins c-akt / genetics, metabolism Pulmonary Alveoli / abnormalities, embryology, enzymology, pathology |
| Grant Support | |
ID/Acronym/Agency:
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HL074832/HL/NHLBI NIH HHS; HL086322/HL/NHLBI NIH HHS; HL092967/HL/NHLBI NIH HHS; HL56594/HL/NHLBI NIH HHS; K12-HD-052954/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Forkhead Transcription Factors; 0/Foxf1a protein, mouse; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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