在正常和纤维性肺组织中识别氨酸化细胞外基质蛋白
Litiele Cezar Cruz1, Aida Habibovic2, Bianca Dempsey3
1Department of Biochemistry, Institute of Chemistry, University of São Paulo, SP, Brazil; Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, VT, USA.
Redox biology
|March 2, 2024
概括
氧化 (PXDN) 通过将化物纳入氨酸残留物来修改细胞外基因蛋白. 这种化发生在正常和纤维化肺组织中,这表明PXDN在ECM调节中的生物学作用.
科学领域:
- 生物化学 生物化学
- 细胞外矩阵生物学 细胞外矩阵生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 氧化素 (PXDN) 是一种被分泌的酶,参与细胞外基质 (ECM) 通过酸 (HOBr) 合成进行交联.
- 此外,PXDN还可能通过将化物纳入氨酸残留物来修改ECM蛋白,这一过程尚未完全理解.
- 识别PXDN目标对于理解其在ECM结构和功能中的作用至关重要.
研究的目的:
- 通过HOBr或PXDN在小鼠细胞中识别主要的ECM蛋白质,这些蛋白质是色素化向的.
- 调查健康和纤维化小鼠以及人类受试者的肺组织中铁素修饰的存在和程度.
- 探索PXDN表达,纤维化和化ECM蛋白之间的关系.
主要方法:
- 基于质谱的蛋白质组学,用于从小鼠PFHR9细胞和肺组织中在ECM中识别含有铁 (BrY) 的.
- 在健康和纤维化小鼠肺部和刺激细胞中分析PXDN和ECM蛋白质表达 (mRNA和蛋白质水平).
- 在不同的条件和物种中比较BrY修饰的ECM蛋白质.
主要成果:
- 在HOBr修饰的ECM中从23种蛋白质中鉴定出61种含BrY的,其中的拉米因表现出明显的化.
- 在未经处理的细胞中检测到胺α1,胺β1和TINAGL1中的BrY,依赖于PXDN.
- 在健康和有纤维的小鼠肺部中发现了11个含BrY的ECM蛋白 (包括原蛋白和拉米林),在人类肺部发现了7个,在纤维化中PXDN表达升高.
结论:
- PXDN调解了几种ECM蛋白的氨酸化,包括氨酸和TINAGL1,即使没有诱导HOBr.
- 在正常的肺组织中存在ECM蛋白的铁修饰,这表明PXDN.的内在生物功能.
- 虽然PXDN和一些ECM蛋白在肺纤维化中被上调,但拉米林化相对程度并没有显著增加.
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