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Published ahead of print on June 22, 2006, doi:10.1165/rcmb.2006-0159OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 35, pp. 611-618, 2006
© 2006 American Thoracic Society
DOI: 10.1165/rcmb.2006-0159OC

Heparin and Fibroblast Growth Factors Affect Surfactant Protein Gene Expression in Type II Cells

Kevin A. Leiner, Donna Newman, Cheng-Ming Li, Eric Walsh, Jody Khosla and Philip L. Sannes

Department of Molecular Biomedical Sciences, Center for Comparative Molecular Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina

Correspondence and requests for reprints should be addressed to Philip L. Sannes, Ph.D., Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606. E-mail: Philip_Sannes{at}ncsu.edu

The stimulation and maintenance of the pulmonary alveolar type II cell's capacity to biosynthesize, store, and secrete surfactant proteins (SPs) are modulated to a great extent by growth factors, extracellular matrix (ECM) components, and hormones. It is possible that differences in ECM composition, as exist between type I and II cells normally or as might occur with excessive cell surface shedding during inflammation or injury states, may specifically alter SP expression. Here, isolated type II cells were exposed to the model sulfated ECM heparin; desulfated heparin; and/or fibroblast growth factor (FGF)-1, -2, or -7 for 24 h to examine by quantitative real-time polymerase chain reaction their effects on SP gene expression. Aquaporin 5 (AQP-5) gene expression was also examined as a phenotypic marker for the type I cell. SP-B mRNA abundance was increased 4- to 8-fold by all three FGFs. Heparin at low concentrations (5 µg/ml) or desulfated heparin at high concentrations (500 µg/ml) enhanced the effects of FGF-2 and -7, while high heparin concentrations (500 µg/ml) were inhibitory. In contrast, SP-B mRNA abundance was increased by heparin in a dose- and sulfation-dependent manner when used in combination with FGF-1. SP-C and AQP-5 mRNA levels were increased by heparin alone in a dose- and sulfation-dependent manner, while all FGFs lacked effect on SP-C or AQP-5 mRNA levels. These data indicate that heparin can be stimulatory to SP gene expression depending on concentration, degree of sulfation, and surrounding FGF environment, and that heparin plays a significant role in modulating alveolar epithelial cell phenotype in vitro.

Key Words: extracellular matrix • fibroblast growth factor • keratinocyte growth factor • surfactant protein-B • surfactant protein-C




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Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. R. Newman, E. Walsh, K. B. C. Apparao, and P. L. Sannes
Fibroblast growth factor-binding protein and N-deacetylase/N-sulfotransferase-1 expression in type II cells is modulated by heparin and extracellular matrix
Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1314 - L1320.
[Abstract] [Full Text] [PDF]




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