Saboor, F., Reckmann, A. N., Tomczyk, C. U., Peters, D. M., Weissmann, N., Kaschtanow, A., Schermuly, R. T., Michurina, T. V., Enikolopov, G., Muller, D., Mietens, A., Middendorff, R. (March 2016) Nestin-expressing vascular wall cells drive development of pulmonary hypertension. Eur Respir J, 47 (3). pp. 876-88. ISSN 1399-3003 (Electronic)0903-1936 (Linking)
Abstract
Nestin, a well-known marker of neuronal stem cells, was recently suggested to characterise stem cell-like progenitors in non-neuronal structures during development and tissue repair. Integrating novel morphological approaches (CLARITY), we investigate whether nestin expression defines the proliferating cell population that essentially drives vascular remodelling during development of pulmonary hypertension.The role of nestin was investigated in lungs of nestin-GFP (green fluorescent protein) mice, models of pulmonary hypertension (rat: monocrotaline, SU5416/hypoxia; mouse: hypoxia), samples from pulmonary hypertension patients and human pulmonary vascular smooth muscle cells (VSMCs).Nestin was solely found in lung vasculature and localised to proliferating VSMCs, but not bronchial smooth muscle cells. Nestin was shown to affect cell number and was significantly enhanced in lungs early during development of pulmonary hypertension, correlating well with increased VSMC proliferation, expression of phosphorylated (activated) platelet-derived growth factor receptor beta and downregulation of the smooth muscle cell differentiation marker calponin. At later time points when pulmonary hypertension became clinically evident, nestin expression and proliferation returned to control levels. Increase of nestin-positive VSMCs was also found in human pulmonary hypertension, both in vessel media and neointima.Nestin expression seems to be obligatory for VSMC proliferation, and specifies lung vascular wall cells that drive remodelling and (re-)generation. Our data promise novel diagnostic tools and therapeutic targets for pulmonary hypertension.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > organs types and functions > lung bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > nestin organs, tissues, organelles, cell types and functions > tissues types and functions > smooth muscle |
| CSHL Authors: | |
| Communities: | CSHL labs > Enikopolov lab |
| Depositing User: | Matt Covey |
| Date: | March 2016 |
| Date Deposited: | 05 Jan 2016 20:25 |
| Last Modified: | 08 Jul 2021 15:46 |
| PMCID: | PMC5796529 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32205 |
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