巨细胞DCLK1通过激活RIP2/TAK1信号通路来促进肥胖引起的心肌病
Bin Yang1,2, Yunjie Zhao2, Wu Luo1,3
1Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
Cell death & disease
|July 13, 2023
概括
巨细胞中双丁类激酶1 (DCLK1) 的过度表达导致肥胖引起的心脏病. 在巨细胞中抑制DCLK1可以保护心脏功能障碍和炎症,揭示了一个新的治疗点.
科学领域:
- 心血管疾病的研究研究.
- 肥胖的分子机制肥胖的分子机制
- 炎症和免疫学 炎症和免疫学
背景情况:
- 肥胖是心血管疾病的主要危险因素,包括由慢性炎症驱动的心肌病.
- 已知癌症标的双丁类激酶1 (DCLK1) 在与肥胖有关的心血管疾病中起不清楚的作用.
研究的目的:
- 调查DCLK1在肥胖引起的心肌病中的作用.
- 确定DCLK1心脏影响中涉及的特定细胞类型和分子通路.
主要方法:
- 生成和分析的DCLK1被删除的小鼠 (巨细胞特异性和心肌细胞特异性淘汰) 食高脂肪饮食 (HFD).
- 利用RNA测序来分析基因表达变化.
- 研究了一种药理学DCLK1抑制剂对HFD养小鼠的影响.
主要成果:
- 宏细胞特异性DCLK1淘汰,而不是心肌细胞特异性淘汰,预防了HFD诱导的心脏功能障碍,缩和纤维化.
- DCLK1缺乏抑制RIP2/TAK1激活和巨细胞的炎症反应.
- 大细胞DCLK1调解RIP2/TAK1酸化,促进炎症,心肌细胞缩和纤维细胞纤维化.
结论:
- 巨细胞DCLK1在肥胖引起的心肌病症中起着促炎作用.
- DCLK1是治疗肥胖相关心脏病的新型治疗点.
相关概念视频
01:38Inflammation
53.9K
Overview
53.9K
01:07MAPK Signaling Cascades
5.7K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
01:22PI3K/mTOR/AKT Signaling Pathway
3.7K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.7K