BAG3通过准INTS7来调节骨髓中酶干细胞的增殖.
Yubo Liu1, Renjie Xu1, Jinfu Xu2
1Department of Orthopaedics, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.
PeerJ
|August 14, 2023
概括
骨髓介质干细胞 (BMMSC) 的扩张是由BAG3蛋白促进的,该蛋白直接与INTS7.7相互作用. BAG3减少了氧化应激,增强了BMMSC的扩散和生存.
科学领域:
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
- 细胞生理学 细胞生理学
背景情况:
- 骨髓介质干细胞 (BMMSCs) 对于组织修复和再生至关重要.
- 众所周知,BAG3蛋白调节细胞存活,并与癌症和心脏病有关.
- 之前的研究表明,BAG3和INTS7之间的潜在相互作用会影响BMMSC的扩散,但直接的约束和监管机制仍然不清楚.
研究的目的:
- 阐明BAG3和INTS7.7之间的直接相互作用.
- 确定BAG3在调节骨髓介质干细胞 (BMMSC) 增殖和扩张中的作用.
- 研究 BAG3 影响 BMMSC 行为的潜在分子机制.
主要方法:
- 定量实时PCR用于评估siRNA淘汰后的BAG3表达.
- 细胞增殖试验 (CCK-8,殖民地形成) 来评估BMMSC的生长.
- 穿越井迁移,流细胞计和TUNEL测试用于分析迁移,细胞循环和细胞亡.
- 共同免疫沉,蛋白质半衰期测定和西部涂抹以确定分子相互作用和机制.
主要成果:
- BAG3的淘汰显著降低了BMMSC的增殖,迁移和殖民地形成,同时诱导了细胞亡和细胞循环停止.
- BAG3与INTS7直接相互作用,由共免疫沉和生物信息学分析证实.
- BAG3的下调导致INTS7的表达减少,INTS7的泛化增加,活性氧物种增加,以及BMMSCs的DNA损伤.
- 过度表达BAG3或INTS7,或使用抗氧化剂,拯救了BAG3对BMMSCs的破坏性影响.
结论:
- BAG3直接与INTS7.7结合在一起.
- BAG3通过减轻氧化应激和DNA损伤来促进BMMSC扩张和生存.
- BAG3-INTS7相互作用是维持BMMSC功能的一个关键调节轴.
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