HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/1/L223    most recent 00159.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Kunzmann, S. Articles by Kramer, B. W. Search for Related Content PubMed PubMed Citation Articles by Kunzmann, S. Articles by Kramer, B. W.

Antenatal inflammation induced TGF-1 but suppressed CTGF in preterm lungs

¹University Children's Hospital, Würzburg, Germany; ²Children's Hospital Medical Center, Cincinnati, Ohio; and ³University Hospital, Maastricht, The Netherlands

Submitted 25 April 2006 ; accepted in final form 4 August 2006

Chorioamnionitis is frequently associated with preterm birth and increases the risk of adverse outcomes such as bronchopulmonary dysplasia (BPD). Transforming growth factor (TGF)-1 is a key regulator of lung development, airway remodeling, lung fibrosis, and regulation of inflammation, and all these processes contribute to the development of BPD. Connective tissue growth factor (CTGF) is a downstream mediator of some of the profibrotic effects of TGF-1, vascular remodeling, and angiogenesis. TGF-1-induced CTGF expression can be blocked by TNF-. We asked whether chorioamnionitis-associated antenatal inflammation would regulate TGF-1, the TGF-1 signaling pathway, and CTGF in preterm lamb lungs. Fetal sheep were exposed to 4 mg of intra-amniotic endotoxin or saline for 5 h, 24 h, 72 h, or 7 days before preterm delivery at 125 days gestation (full term = 150 days). Intra-amniotic endotoxin increased lung TGF-1 mRNA and protein expression. Elevated TGF-1 levels were associated with TGF-1-induced phosphorylation of Smad2. CTGF was selectively expressed in lung endothelial cells in control lungs, and intra-amniotic endotoxin caused CTGF expression to decrease to 30% of control values and TNF- protein to increase. The antenatal inflammation-induced TGF-1 expression and Smad signaling in the fetal lamb lung may contribute to impaired lung alveolarization and reduced lung inflammation. Decreased CTGF expression may inhibit vascular development or remodeling and limit lung fibrosis during remodeling. These effects may contribute to the impaired alveolar and pulmonary vascular development that is the hallmark of the new form of BPD.

chorioamnionitis; bronchopulmonary dysplasia; Smad signaling; fibrosis

This article has been cited by other articles:

				J V Been and L J I Zimmermann Histological chorioamnionitis and respiratory outcome in preterm infants Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2009; 94(3): F218 - F225. [Abstract] [Full Text] [PDF]

				J. T. Colston, S. D. de la Rosa, M. Koehler, K. Gonzales, R. Mestril, G. L. Freeman, S. R. Bailey, and B. Chandrasekar Wnt-induced secreted protein-1 is a prohypertrophic and profibrotic growth factor Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1839 - H1846. [Abstract] [Full Text] [PDF]