区域性和疾病特异性糖氨基成分和功能在脱细胞化人类肺部细胞外基质中
Evan Hoffman1, Yuefan Song2, Fuming Zhang2
1Larner College of Medicine, University of Vermont, 149 Beaumont Avenue, Health Science Research Facility (HSRF) 226, Burlington, VT 05405, USA.
Acta biomaterialia
|July 11, 2023
概括
脱细胞化的肺支架显示了慢性阻塞性肺病 (COPD) 和异常性肺纤维化 (IPF) 肺部的改变糖氨基甘 (GAG) 组成和生长因子结合,影响了肺部生物工程潜力.
科学领域:
- 生物材料科学 生物材料科学
- 再生医学是一种再生医学.
- 肺部生物学 肺部生物学
背景情况:
- 脱细胞化的肺支架对于ex vivo肺生物工程至关重要.
- 肺部的区域异质性和细胞外基质 (ECM) 中的疾病特异性变化尚未完全理解.
- 肺部ECM中的糖氨基酸 (GAG) 影响细胞行为,但它们的区域性和疾病特异性作用需要进一步研究.
研究的目的:
- 确定正常,COPD和IPF患者脱细胞肺的气道,血管和气泡区域的GAG组成和功能的差异.
- 研究这些地区的GAG如何结合关键生长因子和细胞因子.
- 了解ECM GAG改变在肺部疾病中的功能影响.
主要方法:
- 人类肺部从正常,COPD和IPF捐赠者的脱细胞化.
- 在区域肺部区内量化GAG (肝硫酸 (HS),胆素硫酸 (CS),氨酸 (HA)).
- 表面等离子体共振以评估生长因子 (FGF2,TGF-β) 和细胞因子与GAG结合.
- 对GAG分糖化合物组成和硫化模式的分析.
主要成果:
- 在肺部区域和疾病状态之间观察到HS,CS和HA含量和CS/HS组成的显著差异.
- 来自IPF肺部的HS和CS与正常肺和COPD肺相比,显示FGF2和TGF-β的结合减少.
- 细胞因子从IPF的GAG中分离得更快,可能是由于硫化和分糖化合物组成的改变 (例如,在IPF中硫化HS较少,硫化CS较多).
结论:
- 肺 ECM GAG 的区域和疾病特异性差异显著影响生长因子和细胞因子结合.
- 在IPF肺部改变的GAG成分可能会损害它们在肺部生物工程支架中的功能.
- 这些发现增强了对ECM GAG在肺生物学和疾病发病过程中的作用的理解.
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