Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis.

Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Research Abstract Details 

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Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Abstract Text:

William D Hardie,Thomas R Korfhagen,Maureen A Sartor,Adrienne Prestridge,Mario Medvedovic,Timothy D Le Cras,Machiko Ikegami,Scott C Wesselkamper,Cynthia Davidson,Maggie Dietsch,William Nichols,Jeffrey A Whitsett,George D Leikauf,

Expression of transforming growth factor alpha (TGF-alpha) in the respiratory epithelium of transgenic mice caused pulmonary fibrosis, cachexia, pulmonary hypertension, and altered lung function. To identify genes and molecular pathways mediating lung remodeling, mRNA microarray analysis was performed at multiple times after TGF-alpha expression and revealed changes consistent with a role for TGF-alpha in the regulation of extracellular matrix and vasculogenesis. Transcripts for extracellular matrix proteins were augmented along with transcripts for genes previously identified to have roles in pulmonary fibrosis, including tenascin C, osteopontin, and serine (or cysteine) peptidase inhibitor, clade F, member 1. Transcripts regulating vascular processes including endothelin receptor type B, endothelial-specific receptor tyrosine kinase, and caveolin, caveolae protein 1 were decreased. When TGF-alpha expression was no longer induced, lung remodeling partially reversed and lung function and pulmonary hypertension normalized. Transcripts increased during resolution included midkine, matrix metalloproteinase 2, and hemolytic complement. Hierarchical clustering revealed that genes regulated by TGF-alpha were similar to those altered in the lungs of patients with idiopathic pulmonary fibrosis. These studies support a role for epithelial cell-derived TGF-alpha in the regulation of processes that alter the airway and vascular architecture and function.

Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Publishing Authors By Initials

WD Hardie,TR Korfhagen,MA Sartor,A Prestridge,M Medvedovic,TD Le Cras,M Ikegami,SC Wesselkamper,C Davidson,M Dietsch,W Nichols,JA Whitsett,GD Leikauf,

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Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: American journal of respiratory cell and molecular

VOLUME: 37

Page Numbers: 309-21

Journal Abbreviation: Am. J. Respir. Cell Mol. Biol.

ISSN: 1044-1549

DAY: 11

MONTH: 05

YEAR: 2007

Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8917225

Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor alpha

MESH TERMS: physiology

Chemical & Substance for Abstract: Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis. Information

Substance Name: Doxycycline

Registry Number: 564-25-0

Grant and Affiliation Information for Genomic profile of matrix and vasculature remodeling in TGF-alpha induced pulmonary fibrosis.

AFFILIATION: Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229, USA. william.hardie@cchmc.org

Country: United States

AGENCY: United States NHLBI

GRANT: HL72894

ACRONYM: HL

MEDLINETA: Am J Respir Cell Mol Biol

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