在FSTL1中特定于位点的酸化决定了它在伤口愈合中的促进作用
Anagha Priya Suresh1, Monisha Vijayarengan2, Pooja Aggarwal2
1Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka, 570020, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad- 201002, India.
Biochimie
|May 20, 2024
概括
在Serine 165的Follistatin像-1 (FSTL-1) 酸化对于角质细胞迁移和伤口愈合至关重要. 这种新的翻译后修改在糖尿病患者中受损,影响愈合.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 皮肤病学 皮肤病学
背景情况:
- 福利斯塔丁像-1 (FSTL-1) 是一种分泌的葡萄糖蛋白,在皮肤受伤时对角质细胞迁移至关重要.
- 损坏的FSTL-1上调有助于糖尿病足 (DFU) 的不治愈.
- 已知的翻译后修饰 (PTMs),如糖化,对FSTL-1功能至关重要,但其他仍未被探索.
研究的目的:
- 为了在FSTL-1中超出糖基化,识别出新的PTM.
- 为了研究新发现的Serine 165 (S165) 酸化在FSTL-1的前迁移功能中的作用.
- 探索S165酸化对伤口愈合的影响,特别是在糖尿病病例中.
主要方法:
- 质谱学数据的in-silico分析以确定新的PTMs.
- 局部导向的突变发生,以产生酸化缺陷的FSTL-1突变体 (S165A).
- 在体外测试中使用293T细胞和培养的角质细胞来评估FSTL-1分泌,迁移和信号通路 (ERK).
- 在高葡萄糖条件下评估S165酸化水平.
主要成果:
- 在FSTL-1中发现了一种新的PTM,Serine 165 (S165) 酸化.
- S165A突变取消了FSTL-1在角质细胞中的亲迁移效应,可能是通过破坏ERK信号通路.
- 细菌表达的复合FSTL-1抑制了伤口的关闭,强调了酸化的重要性.
- 在高葡萄糖条件下,S165酸化显著下降,与皮细胞迁移受损相关.
结论:
- 在S165的FSTL-1酸化是一种以前未被识别的PTM,对其前迁移功能至关重要.
- 这种酸化对于有效的伤口愈合至关重要,并且在高葡萄糖环境中受损.
- 向FSTL-1酸化为糖尿病足和其他不愈合的伤口提供了潜在的治疗策略.
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