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Mechanical stretch augments PDGF receptor β expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells

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Abstract

With regard to the mechanotransduction mechanisms of vasculature involved in hypertensive diseases, we aimed to identify tyrosine-phosphorylated proteins in pulmonary artery that responded to mechanical stress. Mechanical stretch simultaneously augmented protein-tyrosine phosphorylation in p55, p95, p105, p115, p130, p165, p180 in pulmonary artery tissue and pulmonary artery-derived smooth muscle cells (PASMC), whereas p115 and p55 were preferentially phosphorylated by the stretch in endothelial cells (PAEC). A series of experiments designed to characterize these proteins indicated that p115 and p180 were focal adhesion kinase (FAK) and platelet-derived growth factor receptor β (PDGF-Rβ), respectively, and that stretch augmented the surface-expression of PDGF-Rβ in PASMC but not in PAEC. Moreover, a significant increase in the steady-state mRNA level for PDGF-Rβ was observed in the pulmonary artery of rats with monocrotaline-induced pulmonary hypertension, where the artery should be overstretched due to increasing pulmonary arterial blood pressure. These results suggest that stretch-induced overexpression of cell-surface PDGF-Rβ as well as augmentation of tyrosine phosphorylation of proteins including FAK in PASMC might be involved in the mechanotransduction of pulmonary artery.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, University of Hizuoka, 52-1 Yada, Shizuoka-city, Shizuoka, 422-8526, Japan

    Yoshiyuki Tanabe, Maki Saito, Akiko Ueno & Mariko Nakamura

  2. Laboratory of Genetic Engineering, School of Food and Nutritional Sciences, University of Hizuoka, 52-1 Yada, Shizuoka-city, Shizuoka, 422-8526, Japan

    Keiichi Takeishi

  3. Department of Pharmacology, School of Pharmaceutical Sciences, University of Hizuoka, 52-1 Yada, Shizuoka-city, Shizuoka 422-8526, Japan

    Koichi Nakayama

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  1. Yoshiyuki Tanabe
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Tanabe, Y., Saito, M., Ueno, A. et al. Mechanical stretch augments PDGF receptor β expression and protein tyrosine phosphorylation in pulmonary artery tissue and smooth muscle cells. Mol Cell Biochem 215, 103–113 (2000). https://doi.org/10.1023/A:1026506801659

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