莱特-7c/g下调调节对触发双负反循环和促进复的作用
Qian Zhang1, Xiaojun Zhou2,3, Xianzhi Li3
1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
Chinese medical journal
|July 11, 2023
概括
一个涉及Lin28a和let-7c/let-7g的双负反循环驱动静脉平滑肌细胞在静脉缩中的增殖. 这一发现揭示了糖尿病下肢动脉疾病中的致病机制.
科学领域:
- 血管生物学 血管生物学
- 疾病的分子机制.
- 基因规则 基因规则
背景情况:
- 糖尿病下肢动脉疾病 (LEAD) 中的静脉炎 (RS) 是由过度的血管光滑肌细胞 (VSMC) 增殖和迁移驱动的.
- 在RS中VSMC功能障碍背后的精确致病机制仍然不太清楚.
研究的目的:
- 为了研究调节VSMC增殖和迁移的分子机制,在老鼠模型的复原.
- 探索Lin28a和let-7微RNA在复原病的发病过程中的作用.
主要方法:
- 开发了一种两步伤害老鼠复原模型 (动脉样硬化诱导,然后进行皮肤透光血管造形术).
- 使用EDU和Transwell测定对VSMC扩散和迁移的评估.
- 分析Lin28a和let-7家族成员的表达,通过西式涂抹和qRT-PCR.
- 使用两步转染协议对监管相互作用的调查.
主要成果:
- Lin28a被确定为let-7c,let-7g和miR98.8的调节者.
- 观察到一个反循环,其中减少了let-7c/let-7g表达导致Lin28a增加,进一步抑制了let-7c/let-7g.
- 在回中检测到升高的let-7d水平,这表明它对VSMC的增殖和迁移起着保护作用.
结论:
- 在Lin28a和let-7c/let-7g之间的双负反循环有助于在静脉缩中异常的VSMC行为.
- 这个循环代表了一个潜在的治疗目标,用于管理糖尿病患者的LEAD.
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