Source:http://linkedlifedata.com/resource/pubmed/id/20889544
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2010-10-21
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| pubmed:abstractText |
Hypoxia-induced mitogenic factor (HIMF), also known as found in inflammatory zone 1 and resistin-like molecule ?, belongs to a novel class of cysteine-rich secreted proteins. It exhibits mitogenic and chemotactic properties during pulmonary hypertension-associated vascular remodeling, as well as fibrogenic properties during pulmonary fibrosis. HIMF expression in the lung was reported to be regulated by Th2 cytokines (IL-4 and IL-13) via the transcription factor STAT6 pathway in a bleomycin-induced pulmonary fibrosis model. However, in this study, we found that in the hypoxia-induced pulmonary hypertension model, lung HIMF expression is increased in IL-4 and STAT6 knockout (KO) mice to the same degree as in wild-type (WT) mice, suggesting that induction of HIMF expression does not require Th2 regulation in this model. We also found that HIMF-induced proliferative activity, hypertrophy, collagen, and extracellular matrix deposition in the pulmonary arteries are significantly less in IL-4 KO mice than in WT mice. In addition, HIMF-induced production of angiogenic factors/chemokines, such as vascular endothelial growth factor, MCP-1, and stromal-derived factor-1, in the lung resident cells, as well as macrophage infiltration, were significantly suppressed in the lungs of IL-4 KO mice. We also show that IL-4 was significantly increased in the lungs of HIMF-treated WT mice. Our in vitro studies using pulmonary microvascular endothelial cells revealed that HIMF stimulated cell proliferation, vascular endothelial growth factor expression, and MCP-1 production in a manner that is dependent on the IL-4/IL-4R? system. These findings suggest that IL-4 signaling may play a significant role in HIMF-induced lung inflammation and vascular remodeling.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
185
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5539-48
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| pubmed:meshHeading |
pubmed-meshheading:20889544-Animals,
pubmed-meshheading:20889544-Cell Movement,
pubmed-meshheading:20889544-Cell Proliferation,
pubmed-meshheading:20889544-Endothelial Cells,
pubmed-meshheading:20889544-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:20889544-Extracellular Matrix,
pubmed-meshheading:20889544-Gene Expression,
pubmed-meshheading:20889544-Gene Expression Regulation,
pubmed-meshheading:20889544-Hypertension, Pulmonary,
pubmed-meshheading:20889544-Immunoblotting,
pubmed-meshheading:20889544-Immunohistochemistry,
pubmed-meshheading:20889544-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:20889544-Interleukin-4,
pubmed-meshheading:20889544-Lung,
pubmed-meshheading:20889544-Male,
pubmed-meshheading:20889544-Mice,
pubmed-meshheading:20889544-Mice, Inbred C57BL,
pubmed-meshheading:20889544-Mice, Knockout,
pubmed-meshheading:20889544-Organ Culture Techniques,
pubmed-meshheading:20889544-Pneumonia,
pubmed-meshheading:20889544-Pulmonary Fibrosis,
pubmed-meshheading:20889544-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20889544-Signal Transduction
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| pubmed:year |
2010
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| pubmed:articleTitle |
Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMalpha) increases lung inflammation and activates pulmonary microvascular endothelial cells via an IL-4-dependent mechanism.
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| pubmed:affiliation |
Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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