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Over-expression of PDGF-C using a lung specific promoter results in abnormal lung development

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Abstract

PDGF isoforms are a family of polypeptides that bind to cell surface receptors and induce fibroblast proliferation and chemotaxis. PDGF-A and -B chain isoforms have previously been shown to be involved in murine lung development. A new PDGF polypeptide, PDGF-C, was recently recognized and differs from the PDGF-A and -B isoforms in that it requires proteolytic cleavage before it can bind and activate the PDGF alpha receptor. In these studies PDGF-C was over-expressed during embryogenesis using the lung specific surfactant protein C promoter. PDGF-C transgenic pups died from respiratory insufficiency within minutes following birth. At E18.5, nontransgenic lungs exhibited lung morphology consistent with the saccular stage of lung development. In contrast, E18.5 transgenic lungs retained many features of the canalicular stage of lung development and had abundant numbers of large poorly differentiated mesenchymal cells. These results suggest that PDGF-C is activated during lung development and is a potent growth factor for mesenchymal cells in vivo.

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Acknowledgments

This work was supported by the National Heart Lung and Blood Institute R01-HL63778 and the National Institute of Environmental Health Sciences ES10046. We also acknowledge the continued support of the Tulane/Xavier Center for Bioenvironmental Research and the Tulane Cancer Center.

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Authors and Affiliations

  1. Departments of Medicine and Pathology , Tulane University Health Sciences Center , 1430 Tulane Avenue, New Orleans, LA, 70112, USA

    Ying Zhuo, Gary W. Hoyle, Bin Shan, Dawn R. Levy & Joseph A. Lasky

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  1. Ying Zhuo
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  2. Gary W. Hoyle
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  3. Bin Shan
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  4. Dawn R. Levy
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  5. Joseph A. Lasky
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Correspondence to Joseph A. Lasky.

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Zhuo, Y., Hoyle, G.W., Shan, B. et al. Over-expression of PDGF-C using a lung specific promoter results in abnormal lung development. Transgenic Res 15, 543–555 (2006). https://doi.org/10.1007/s11248-006-9007-5

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  • DOI: https://doi.org/10.1007/s11248-006-9007-5

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