CGRP alleviates lipopolysaccharide-induced ARDS inflammation via the HIF-1α signaling pathway.

IF 7.7 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Renzi Zhang, Yuhua Zhong, Qiudie Liu, Mengqi Zhang, Daoxin Wang, Sheng Li, Di Qi
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引用次数: 0

Abstract

Acute respiratory distress syndrome (ARDS) is an acute and severe disease with a high mortality rate. The outbreak of immune inflammation in the lung is an important pathogenic mechanism of ARDS. Notably, an imbalance in macrophage polarization is an important link in the occurrence and development of this inflammatory response. Recently, neuropeptides have been shown to regulate inflammation, but the role of neuropeptides in ARDS remains unclear. The aim of this study was to investigate the regulatory effect of calcitonin gene-related peptide (CGRP) on the inflammatory response in ARDS. We found that CGRP expression was increased in the serum of ARDS patients and in both in vitro and in vivo models of ARDS. CGRP can regulate the polarization of macrophages by targeting its receptor (receptor activity-modifying protein 1); reduce the proportion of M1 macrophages; increase the proportion of M2 macrophages; and reduce pathological injury, inflammation, oxidative stress, and apoptosis in lung tissue in LPS-induced ARDS both in vitro and in vivo. Additionally, we performed transcriptome sequencing and found that hypoxia-inducible factor-1α (HIF-1α) is involved in the above process and that CGRP can alleviate ARDS-related pathological damage, inflammation, and oxidative stress by inhibiting the HIF-1α pathway to regulate macrophage polarization balance. These results indicate that CGRP has good potential for clinical translation in the treatment of pulmonary infection in ARDS. Furthermore, this study provides new ideas for the treatment of inflammatory bursts in ARDS.

CGRP通过HIF-1α信号通路减轻脂多糖诱导的ARDS炎症。
急性呼吸窘迫综合征(ARDS)是一种死亡率高的急性重症疾病。肺部免疫性炎症的爆发是ARDS的重要致病机制。值得注意的是,巨噬细胞极化失衡是这种炎症反应发生和发展的重要环节。最近,神经肽已被证明可以调节炎症,但神经肽在ARDS中的作用尚不清楚。本研究旨在探讨降钙素基因相关肽(CGRP)对ARDS炎症反应的调节作用。我们发现CGRP在ARDS患者血清及ARDS体外和体内模型中的表达均升高。CGRP通过靶向其受体(受体活性修饰蛋白1 (receptor activity修饰protein 1, RAMP1))调节巨噬细胞的极化,降低M1巨噬细胞比例,增加M2巨噬细胞比例,在体外和体内均可减轻lps诱导的ARDS肺组织的病理损伤、炎症、氧化应激和凋亡。此外,我们通过转录组测序发现,缺氧诱导因子-1α (HIF-1α)参与了上述过程,CGRP通过抑制HIF-1α通路调节巨噬细胞极化平衡,从而减轻ards相关的病理损伤、炎症和氧化应激。这些结果表明,CGRP在ARDS肺部感染治疗中具有良好的临床转化潜力。本研究为急性呼吸窘迫综合征炎症发作的治疗提供了新的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical science
Clinical science 医学-医学:研究与实验
CiteScore
11.40
自引率
0.00%
发文量
189
审稿时长
4-8 weeks
期刊介绍: Translating molecular bioscience and experimental research into medical insights, Clinical Science offers multi-disciplinary coverage and clinical perspectives to advance human health. Its international Editorial Board is charged with selecting peer-reviewed original papers of the highest scientific merit covering the broad spectrum of biomedical specialities including, although not exclusively: Cardiovascular system Cerebrovascular system Gastrointestinal tract and liver Genomic medicine Infection and immunity Inflammation Oncology Metabolism Endocrinology and nutrition Nephrology Circulation Respiratory system Vascular biology Molecular pathology.
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