可溶性二基-4酶通过瘤生长因子-β受体诱导表皮细胞-介质细胞过渡
Cheng-Wei Huang1, Shih-Yi Lee2,3, Chen-Xuan Du1
1Department of Life Science, Fu Jen Catholic University, No.510, Zhongzheng Road, Xinzhuang District, New Taipei City, 242, Taiwan.
Pharmacological reports : PR
|May 26, 2023
概括
溶性二乙酸-4 (sDPP4) 通过诱导细胞中表皮质-介质细胞过渡 (EMT) 来促进纤维化. 针对sDPP4/TGFBR/SMAD通路使用linagliptin等DPP4抑制剂可能会预防纤维化.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 纤维化是慢性病的后果,涉及炎症和细胞外基质沉积.
- 皮质-介质细胞过渡 (EMT) 通过改变细胞特征,有助于组织纤维化.
- 在代谢综合征中,可溶性二二酶-4 (sDPP4) 水平发生变化,但其在脏EMT中的作用尚不清楚.
研究的目的:
- 为了研究可溶性二二酸-4 (sDPP4) 对上皮细胞的影响.
- 阐明sDPP4影响上皮细胞的分子机制.
- 评估DPP4抑制在减轻sDPP4诱导影响方面的潜力.
主要方法:
- 评估EMT标记物和细胞外基质 (ECM) 蛋白的表达.
- 研究了SMAD信号激活及其对TGFBR的依赖.
- 利用遗传学和药理学方法来准TGFBR.
- 评估了linagliptin,一个DPP4抑制剂,对sDPP4诱导的EMT的影响.
主要成果:
- sDPP4上调了EMT标记物 (ACTA2,COL1A1) 和增加了原蛋白含量.
- 在上皮细胞中,sDPP4通过TGFBR激活SMAD信号传递.
- 抑制TGFBR阻断了sDPP4诱导的SMAD信号传递和EMT.
- 利纳吉普丁取消了sDPP4诱导的EMT.
结论:
- sDPP4/TGFBR/SMAD轴驱动上皮细胞中的EMT.
- 增加sDPP4可能会导致纤维化.
- 抑制DPP4是一种潜在的治疗策略,可以预防纤维化.
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