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: 289/1/L34    most recent 00407.2004v1 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 (2) Citing Articles via Google Scholar Google Scholar Articles by Ikegami, M. Articles by Korfhagen, T. R. Search for Related Content PubMed PubMed Citation Articles by Ikegami, M. Articles by Korfhagen, T. R.

TGF- perturbs surfactant homeostasis in vivo

¹Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio; and ²Department of Pediatrics, Vanderbilt University, Nashville, Tennessee

Submitted 2 November 2004 ; accepted in final form 9 March 2005

To determine potential relationships between transforming growth factor (TGF)- and surfactant homeostasis, the metabolism, function, and composition of surfactant phospholipid and proteins were assessed in transgenic mice in which TGF- was expressed in respiratory epithelial cells. Secretion of saturated phosphatidylcholine was decreased 40–60% by expression of TGF-. Although SP-A, SP-B, and SP-C mRNA levels were unchanged by expression of TGF-, SP-A and SP-B content in bronchoalveolar lavage fluid was decreased. The minimum surface tension of surfactant isolated from the transgenic mice was significantly increased. Incubation of cultured normal mice type II cells with TGF- in vitro did not change secretion of surfactant phosphatidylcholine and SP-B, indicating that TGF- does not directly influence surfactant secretion. Expression of a dominant negative (mutant) EGF receptor in the respiratory epithelium blocked the TGF--induced changes in lung morphology and surfactant secretion, indicating that EGF receptor signaling in distal epithelial cells was required for TGF- effects on surfactant homeostasis. Because many epithelial cells were embedded in fibrotic lesions caused by TGF-, changes in surfactant homeostasis may at least in part be influenced by tissue remodeling that results in decreased surfactant secretion. The number of nonembedded type II cells was decreased 30% when TGF- was expressed during development and was increased threefold by TGF- expression in adulthood, suggesting possible alteration of type II cells on surfactant metabolism in the adult lung. Abnormalities in surfactant function and decreased surfactant level in the airways may contribute to the pathophysiology induced by TGF- in both the developing and adult lung.

bronchopulmonary dysplasia; acute respiratory distress syndrome; pulmonary fibrosis; surface activity of surfactant

This article has been cited by other articles:

				T. Weng, Z. Chen, N. Jin, L. Gao, and L. Liu Gene expression profiling identifies regulatory pathways involved in the late stage of rat fetal lung development Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1027 - L1037. [Abstract] [Full Text] [PDF]