Bian Jingwei, Zhu Yuzhong, Tian Panhui, Yang Qiqi, Li Zijian
Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Beijing Key Laboratory of Cardiovascular Receptors Research; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Cell Signal. 2024 May;117:111124. doi: 10.1016/j.cellsig.2024.111124. Epub 2024 Feb 27.
Overwhelming macrophage M1 polarization induced by malfunction of the renin-angiotensin-aldosterone system (RAAS) initiates inflammatory responses, which play a crucial role in various cardiovascular diseases. However, the underlying regulatory mechanism remains elusive. Here, we identified adaptor protein HIP-55 as a critical regulator of macrophage M1 polarization. The expression of HIP-55 was upregulated in M1 macrophage induced by Ang II. Overexpression of HIP-55 significantly promoted Ang II-induced macrophage M1 polarization, whereas genetic deletion of HIP-55 inhibited the Ang II-induced macrophage M1 polarization. Mechanistically, HIP-55 facilitated activator protein-1 (AP-1) complex activation induced by Ang II via promoting ERK1/2 and JNK phosphorylation. Moreover, blocking AP-1 complex activation can attenuate the function of HIP-55 in macrophage polarization. Collectively, our results reveal the role of HIP-55 in macrophage polarization and provide potential therapeutic insights for cardiovascular diseases associated with RAAS dysfunction.
肾素-血管紧张素-醛固酮系统（RAAS）功能失调诱导的巨噬细胞M1极化过度会引发炎症反应，这在各种心血管疾病中起着关键作用。然而，其潜在的调控机制仍不清楚。在此，我们确定衔接蛋白HIP-55是巨噬细胞M1极化的关键调节因子。在Ang II诱导的M1巨噬细胞中，HIP-55的表达上调。HIP-55的过表达显著促进了Ang II诱导的巨噬细胞M1极化，而HIP-55的基因缺失则抑制了Ang II诱导的巨噬细胞M1极化。机制上，HIP-55通过促进ERK1/2和JNK磷酸化，促进了Ang II诱导的活化蛋白-1（AP-1）复合物的激活。此外，阻断AP-1复合物的激活可减弱HIP-55在巨噬细胞极化中的功能。总的来说，我们的结果揭示了HIP-55在巨噬细胞极化中的作用，并为与RAAS功能障碍相关的心血管疾病提供了潜在的治疗思路。
