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PDGF and microvessel wall remodeling in adult rat lung: imaging PDGF-AA and PDGF-Rα molecules in progenitor smooth muscle cells developing in experimental pulmonary hypertension

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Abstract

Smooth muscle cells are mostly absent from the walls of microvessels in the adult lung but develop in large numbers as part of the pathology of human and experimental pulmonary hypertensions (PHs). We have previously shown, in an in vivo model of experimental PH, that mesenchymal (interstitial) fibroblasts and intermediate cells are the progenitors of these cells. Although smooth muscle cell development is a defining pathophysiological feature of human PH, little is known about the angiogenic signaling molecules responsible. Here, we report data for platelet-derived growth factor AA (PDGF-AA) and PDGF-Rα, two components of an important signaling pathway for fibroblast and myofibroblast proliferation and migration. Using antibodies linked to protein-A gold and high-resolution imaging techniques, we analyzed the expression of these molecules as smooth muscle cells developed from progenitor cell populations and in endothelial cells of the same microvessels. PDGF-AA was highly expressed by each cell type in control lung. As PH developed, the number of antigenic sites for PDGF-AA decreased with time. PDGF-Rα expression levels in the control lung were low, relative to the ligand, and fell in PH. These data show, for the first time, a marked phenotypic shift in expression levels of the PDGF-AA isoform and its receptor tyrosine kinase in the progenitor smooth muscle cells developing in the microvessels of the adult hypertensive lung.

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Authors and Affiliations

  1. Department of Anesthesia and Critical Care, Harvard Medical School and Massachusetts General Hospital, MGH-East, Building 149, 13th Street, Charlestown, MA, 02129, USA

    Rosemary Jones, Diane Capen & Margaretha Jacobson

  2. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, 02114, USA

    Lance Munn

Authors
  1. Rosemary Jones
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  2. Diane Capen
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  3. Margaretha Jacobson
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  4. Lance Munn
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Corresponding author

Correspondence to Rosemary Jones.

Additional information

These studies were supported by NIH 5RO1HL070866 and 5RO1HL064240.

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Jones, R., Capen, D., Jacobson, M. et al. PDGF and microvessel wall remodeling in adult rat lung: imaging PDGF-AA and PDGF-Rα molecules in progenitor smooth muscle cells developing in experimental pulmonary hypertension. Cell Tissue Res 326, 759–769 (2006). https://doi.org/10.1007/s00441-006-0177-5

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