The role and mechanism of endothelial cell-specific molecule-1 in respiratory diseases

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.