The role of hyaluronan synthase 3 in ventilator-induced lung injury

Kuan Jen Bai, Andrew P. Spicer, Marcella M. Mascarenhas, Lunyin Yu, Cristhiaan D. Ochoa, Hari G. Garg, Deborah A. Quinn

研究成果: 雜誌貢獻文章同行評審

105 引文 斯高帕斯(Scopus)


We recently found that low-molecular-weight hyaluronan was induced by cyclic stretch in lung fibroblasts and accumulated in lungs from animals with ventilator-induced lung injury. The low-molecular-weight hyaluronan produced by stretch increased interleukin-8 production in epithelial cells, and was accompanied by an upregulation of hyaluronan synthase-3 mRNA. We hypothesized that low-molecular-weight hyaluronan induced by high VT was dependent on hyaluronan synthase 3, and was associated with ventilator-induced lung injury. Effects of high VT ventilation in C57BL/6 wild-type and hyaluronan synthase-3 knockout mice were compared. Significantly increased neutrophil infiltration, macrophage inflammatory protein-2 production, and lung microvascular leak were found in wild-type animals ventilated with high V T. These reactions were significantly reduced in hyaluronan synthase-3 knockout mice, except the capillary leak. Wild-type mice ventilated with high VT were found to have increased low-molecular-weight hyaluronan in lung tissues and concomitant increased expression of hyaluronan synthase-3 mRNA, neither of which was found in hyaluronan synthase-3 knockout mice. We conclude that high VT induced low-molecular-weight hyaluronan production is dependent on de novo synthesis through hyaluronan synthase 3, and plays a role in the inflammatory response of ventilator-induced lung injury.
頁(從 - 到)92-98
期刊American Journal of Respiratory and Critical Care Medicine
出版狀態已發佈 - 7月 1 2005

ASJC Scopus subject areas

  • 肺和呼吸系統醫學


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