Papakonstantinou E, Karakiulakis G, Tamm M, Perruchoud A P, Roth M
Department of Pharmacology, School of Medicine, Aristotle University, 54006 Thessaloniki, Greece.
Am J Physiol Lung Cell Mol Physiol. 2000 Nov;279(5):L825-34. doi: 10.1152/ajplung.2000.279.5.L825.
Hypoxia, a consequence of interstitial lung diseases, may lead to secondary pulmonary hypertension and pulmonary vascular remodeling. Hypoxia induces activation and proliferation of lung cells and enhances the deposition of extracellular matrix including glycosaminoglycans (GAGs). To elucidate the cell biological mechanisms underlying the development of secondary pulmonary hypertension, we studied the effect of hypoxia on GAG synthesis by human lung cells. GAG synthesis was measured by incorporation of [(3)H]glucosamine; GAGs were isolated, purified, and characterized with GAG-degrading enzymes. Fibroblasts and vascular smooth muscle cells (VSMCs) synthesized hyaluronic acid, heparan sulfate, and chondroitin sulfates, whereas dermatan sulfate was found only in fibroblasts. Hypoxia did not influence the size or charge of the individual GAGs. However, hypoxia inhibited platelet-derived growth factor-induced [(3)H]glucosamine incorporation in secreted GAGs, especially hyaluronic acid, in VSMCs. In contrast, it stimulated GAG secretion, specifically heparan sulfate, by fibroblasts. Our results indicate that hypoxia induces modifications in GAG synthesis by human lung VSMCs and fibroblasts that may be correlated to pathophysiological manifestations in lung diseases causing hypoxia.
缺氧是间质性肺疾病的一个后果，可能导致继发性肺动脉高压和肺血管重塑。缺氧会诱导肺细胞的激活和增殖，并增强包括糖胺聚糖（GAGs）在内的细胞外基质的沉积。为了阐明继发性肺动脉高压发生发展的细胞生物学机制，我们研究了缺氧对人肺细胞GAG合成的影响。通过掺入[³H]葡糖胺来测量GAG合成；用GAG降解酶分离、纯化并鉴定GAGs。成纤维细胞和血管平滑肌细胞（VSMC）合成透明质酸、硫酸乙酰肝素和硫酸软骨素，而硫酸皮肤素仅在成纤维细胞中发现。缺氧不影响单个GAGs的大小或电荷。然而，缺氧抑制血小板衍生生长因子诱导的VSMC中分泌型GAGs（尤其是透明质酸）掺入[³H]葡糖胺。相反，它刺激成纤维细胞分泌GAGs，特别是硫酸乙酰肝素。我们的结果表明，缺氧会诱导人肺VSMC和成纤维细胞中GAG合成的改变，这可能与导致缺氧的肺部疾病的病理生理表现相关。
