Zeng Zhao, Inoue Koichi, Sun Huawei, Leng Tiandong, Feng Xuechao, Zhu Li, Xiong Zhi-Gang
Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Ministry of Health Key Laboratory of Thrombosis and Hemostasis, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China; and Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia.
Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia.
Am J Physiol Cell Physiol. 2015 Feb 15;308(4):C308-18. doi: 10.1152/ajpcell.00275.2013. Epub 2014 Dec 3.
Transient receptor potential melastatin 7 (TRPM7) is a nonselective cation channel with an α-kinase domain in its COOH terminal, known to play a role in diverse physiological and pathological processes such as Mg2+ homeostasis, cell proliferation, and hypoxic neuronal injury. Increasing evidence suggests that TRPM7 contributes to the physiology/pathology of vascular systems. For example, we recently demonstrated that silencing TRPM7 promotes growth and proliferation and protects against hyperglycemia-induced injury in human umbilical vein endothelial cells (HUVECs). Here we investigated the potential effects of TRPM7 on morphology, adhesion, migration, and tube formation of vascular endothelial cells and the potential underlying mechanism. We showed that inhibition of TRPM7 function in HUVECs by silencing TRPM7 decreases the density of TRPM7-like current and cell surface area and inhibits cell adhesion to Matrigel. Silencing TRPM7 also promotes cell migration, wound healing, and tube formation. Further studies showed that the extracellular signal-regulated kinase (ERK) pathway is involved in the change of cell morphology and the increase in HUVEC migration induced by TRPM7 silencing. We also demonstrated that silencing TRPM7 enhances the phosphorylation of myosin light chain (MLC) in HUVECs, which might be involved in the enhancement of cell contractility and motility. Collectively, our data suggest that the TRPM7 channel negatively regulates the function of vascular endothelial cells. Further studies on the underlying mechanism may facilitate the development of the TRPM7 channel as a target for the therapeutic intervention of vascular diseases.
瞬时受体电位褪黑素7（TRPM7）是一种非选择性阳离子通道，其COOH末端具有α激酶结构域，已知在多种生理和病理过程中发挥作用，如镁离子稳态、细胞增殖和缺氧性神经元损伤。越来越多的证据表明，TRPM7参与了血管系统的生理/病理过程。例如，我们最近证明，沉默TRPM7可促进人脐静脉内皮细胞（HUVECs）的生长和增殖，并保护其免受高血糖诱导的损伤。在此，我们研究了TRPM7对血管内皮细胞形态、黏附、迁移和管腔形成的潜在影响及其潜在机制。我们发现，通过沉默TRPM7抑制HUVECs中TRPM7的功能，可降低TRPM7样电流的密度和细胞表面积，并抑制细胞与基质胶的黏附。沉默TRPM7还可促进细胞迁移、伤口愈合和管腔形成。进一步研究表明，细胞外信号调节激酶（ERK）通路参与了TRPM7沉默诱导的细胞形态变化和HUVEC迁移增加。我们还证明，沉默TRPM7可增强HUVECs中肌球蛋白轻链（MLC）的磷酸化，这可能与细胞收缩性和运动性的增强有关。总的来说，我们的数据表明TRPM7通道对血管内皮细胞的功能起负调节作用。对其潜在机制的进一步研究可能有助于将TRPM7通道开发为血管疾病治疗干预的靶点。
