Universität zu Köln

Alcazar, Miguel Angel Alejandre, Morty, Rory E., Lendzian, Lisa, Vohlen, Christina, Oestreicher, Iris, Plank, Christian, Schneider, Holm and Doetsch, Joerg (2011). Inhibition of TGF-beta Signaling and Decreased Apoptosis in IUGR-Associated Lung Disease in Rats. PLoS One, 6 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Intrauterine growth restriction is associated with impaired lung function in adulthood. It is unknown whether such impairment of lung function is linked to the transforming growth factor (TGF)-beta system in the lung. Therefore, we investigated the effects of IUGR on lung function, expression of extracellular matrix (ECM) components and TGF-beta signaling in rats. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 70. Pulmonary activity of the TGF-beta system was determined at P1 and P70. TGF-beta signaling was blocked in vitro using adenovirus-delivered Smad7. At P70, respiratory airway compliance was significantly impaired after IUGR. These changes were accompanied by decreased expression of TGF-beta 1 at P1 and P70 and a consistently dampened phosphorylation of Smad2 and Smad3. Furthermore, the mRNA expression levels of inhibitors of TGF-beta signaling (Smad7 and Smurf2) were reduced, and the expression of TGF-beta-regulated ECM components (e. g. collagen I) was decreased in the lungs of IUGR animals at P1; whereas elastin and tenascin N expression was significantly upregulated. In vitro inhibition of TGF-beta signaling in NIH/3T3, MLE 12 and endothelial cells by adenovirus-delivered Smad7 demonstrated a direct effect on the expression of ECM components. Taken together, these data demonstrate a significant impact of IUGR on lung development and function and suggest that attenuated TGF-beta signaling may contribute to the pathological processes of IUGR-associated lung disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Alcazar, Miguel Angel Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Morty, Rory E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lendzian, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Oestreicher, Iris UNSPECIFIED UNSPECIFIED UNSPECIFIED Plank, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Holm UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-487139
DOI:	10.1371/journal.pone.0026371
Journal or Publication Title:	PLoS One
Volume:	6
Number:	10
Date:	2011
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTRAUTERINE GROWTH-RETARDATION; MOUSE LUNG; TRANSFORMING GROWTH-FACTOR-BETA-1; MATRIX METALLOPROTEINASE-1; BRANCHING MORPHOGENESIS; PLACENTAL INSUFFICIENCY; DEVELOPMENTAL ORIGINS; RESPIRATORY HEALTH; TISSUE INHIBITORS; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48713