内皮细胞特异性分子-1在呼吸系统疾病中的作用及机制

文献信息

中文摘要

内皮细胞特异性分子-1（ESM1）是一种可溶性硫酸皮肤素蛋白聚糖，主要表达于肺内皮细胞。据报道，ESM1在促进细胞增殖（如代谢重编程）和抑制自噬方面发挥重要作用。此外，ESM1对炎症具有双重调节作用。然而，ESM1对炎症双重调节作用的机制仍不清楚。此外，有证据表明ESM1参与多种信号通路，如EGFR/ESM1、EGFR/HER3-Akt/ANGPT2、HGF/c-MET、VEGF-A/ESM1、mTOR和ZEB1/PI3K/AKT通路。越来越多的研究表明，ESM1参与多种呼吸系统疾病，如肺癌、阻塞性睡眠呼吸暂停低通气综合征（OSAHS）、肺动脉高压（PAH）和急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）。在肺癌中，ESM1通过EGFR、NF-κB和HGF/c-MET信号通路促进癌细胞增殖。在OSAHS中，ESM1通过HIF-1α/VEGF信号通路增强炎症因子分泌和单核细胞-内皮细胞黏附。在PAH中，ESM1可能通过与TNF-α的正反馈环路促进血管重塑和炎症。相反，在ALI/ARDS中，ESM1可能抑制白细胞募集以减轻炎症。然而，ESM1在慢性阻塞性肺疾病（COPD）、哮喘和肺炎中的具体作用和机制仍需进一步探索。因此，ESM1可能作为多种呼吸系统疾病的潜在治疗靶点。

英文摘要

Endothelial cell-specific molecule-1 (ESM1) is a soluble dermatan sulfate proteoglycan and is mainly expressed in pulmonary endothelial cells. It is reported that ESM1 plays an important role in promoting cell proliferation, such as metabolic reprogramming, and inhibiting autophagy. In addition, ESM1 exerts a dual regulatory effect on inflammation. However, the mechanism of the dual regulatory effect of ESM1 on inflammation remains unclear. Moreover, evidence suggests that ESM1 is involved in multiple signaling pathways, such as the EGFR/ESM1, EGFR/HER3-Akt/ANGPT2, HGF/c-MET, VEGF-A/ESM1, mTOR, and ZEB1/PI3K/AKT pathways. Increasing studies suggested that ESM1 is involved in various respiratory diseases, such as lung cancer, obstructive sleep apnea hypopnea syndrome (OSAHS), pulmonary arterial hypertension (PAH), and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). In lung cancer, ESM1 promotes cancer cell proliferation through the EGFR, NF-κB, and HGF/c-MET signaling pathways. In OSAHS, ESM1 enhances inflammatory factor secretion and monocyte-endothelial cell adhesion through the HIF-1α/VEGF signaling pathway. In PAH, ESM1 may promote vascular remodeling and inflammation via a positive feedback loop with TNF-α. Conversely, in ALI/ARDS, ESM1 may inhibit leukocyte recruitment to reduce inflammation. However, the specific roles and mechanisms of ESM1 in chronic obstructive pulmonary disease (COPD), asthma, and pneumonia need to be further explored. Accordingly, ESM1 may serve as a potential therapeutic target for various respiratory diseases.