细胞外矩阵硬度通过Igfbp3/Smad途径加剧尿道狭窄
Kaixuan Li1,2,3, Ke Ding2,3, Quan Zhu2,3
1Department of Cardiac Surgery, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Scientific reports
|August 31, 2023
概括
增加尿道矩阵刚度驱动纤维细胞变化在狭窄. Igfbp3/Smad通路调节了这种进展,为尿道纤维化提供了潜在的治疗点.
科学领域:
- 泌尿器科 泌尿器科 泌尿器科 泌尿器科
- 生物材料科学 生物材料科学
- 细胞生物学 细胞生物学
背景情况:
- 尿道狭窄,尿道狭窄,通常是由炎症引起的,但其进展机制尚不清楚.
- 以前的研究表明炎症起作用,但导致尿道纤维化的物理和分子因素仍然不清楚.
研究的目的:
- 调查矩阵度在尿道狭窄进展中的作用.
- 在尿道狭窄中,确定涉及性诱导的纤维细胞到肌纤维细胞过渡 (FMT) 的分子途径.
主要方法:
- 原子力显微镜 (AFM) 用于测量人类和老鼠模型中的尿道矩阵刚度.
- 聚烯胺水凝模仿了不同的矩阵刚度来研究大鼠尿道纤维细胞.
- RNA测序 (RNA-seq) 分析了基因表达变化,重点关注Igfbp3/Smad途径.
主要成果:
- 与正常组织 (5.23 kPa) 相比,尿道狭窄组织表现出明显更高的矩阵刚度 (41.59 kPa).
- 增加的矩阵刚度促进了纤维细胞到肌纤维细胞过渡 (FMT),由增强的α-SMA和原I表达证明.
- 抑制Igfbp3阻断了硬度诱导的FMT并降低了p-Smad2/3水平,而Igfbp3过度表达促进了FMT.
结论:
- 矩阵刚度是尿道狭窄的进展的一个关键因素.
- 该Igfbp3/Smad通路与调节硬度驱动的FMT和尿道纤维化有关.
- 准Igfbp3/Smad通路为尿道狭窄提供了一个有前途的治疗策略.
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