Adropin decreases endothelial monolayer permeability after cell-free hemoglobin exposure and reduces MCP-1-induced macrophage transmigration.
Adropin decreases endothelial monolayer permeability after cell-free hemoglobin exposure and reduces MCP-1-induced macrophage transmigration.
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Adropin降低无细胞血红蛋白暴露后的内皮单层通透性，并减少MCP-1诱导的巨噬细胞迁移。
DOI：
10.1016/j.bbrc.2021.10.032
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发表时间：
2021-12-10
影响因子：
3.1
通讯作者：
Hoh BL
中科院分区：
文献类型：
--
作者：
Dodd WS;Patel D;Lucke-Wold B;Hosaka K;Chalouhi N;Hoh BL
在包括蛛网膜下腔出血和败血症在内的多种疾病状态中，含血红素的无细胞蛋白通过增加内皮通透性介导内皮损伤。炎症细胞也被单核细胞趋化蛋白1（MCP-1）和其他趋化因子吸引到血管损伤部位。我们已经确定了一种新的肽激素，adropin，保护对血红蛋白诱导的内皮细胞通透性和MCP-1诱导的巨噬细胞迁移。人微血管内皮细胞暴露于无细胞血红蛋白（CFH）与Adropin治疗和无细胞血红蛋白治疗之前，使用FITC-葡聚糖示踪剂测定单层渗透性。收集mRNA和培养基用于分子研究。我们还使用MCP-1诱导的迁移试验评估了Adropin对巨噬细胞穿过内皮单层移动的影响。CFH暴露降低adropin表达并增加人内皮细胞的细胞旁通透性。用合成的肾上腺素处理细胞可以防止在自然损伤进展期间观察到的渗透性增加。所有组的细胞活力相似，Adropin处理不影响Hmox 1表达。MCP-1可有效诱导巨噬细胞迁移穿过内皮细胞单层，而Adropin治疗可有效减少这种现象。内皮损伤是许多疾病状态的标志。我们的研究结果表明，肾上腺素治疗可能是一个有价值的策略，在防止血红素介导的内皮损伤和巨噬细胞浸润。需要在动物模型和人体组织标本中进一步研究肾上腺素治疗。
Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial permeability. Inflammatory cells are also attracted to sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other chemokines. We have identified a novel peptide hormone, adropin, that protects against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage migration. Human microvascular endothelial cells were exposed to cell-free hemoglobin (CFH) with and without adropin treatment before measuring monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media were collected for molecular studies. We also assessed the effect of adropin on macrophage movement across the endothelial monolayer using an MCP-1-induced migration assay. CFH exposure decreases adropin expression and increases paracellular permeability of human endothelial cells. Treating cells with synthetic adropin protects against the increased permeability observed during the natural injury progression. Cell viability was similar in all groups and Hmox1 expression was not affected by adropin treatment. MCP-1 potently induced macrophage migration across the endothelial monolayer and adropin treatment effectively reduced this phenomenon. Endothelial injury is a hallmark of many disease states. Our results suggest that adropin treatment could be a valuable strategy in preventing heme-mediated endothelial injury and macrophage infiltration. Further investigation of adropin therapy in animal models and human tissue specimens is needed.
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影响因子：
29
作者：
Kumar KG;Trevaskis JL;Lam DD;Sutton GM;Koza RA;Chouljenko VN;Kousoulas KG;Rogers PM;Kesterson RA;Thearle M;Ferrante AW Jr;Mynatt RL;Burris TP;Dong JZ;Halem HA;Culler MD;Heisler LK;Stephens JM;Butler AA
通讯作者：
Butler AA
影响因子：
5.6
作者：
Sato K;Yamashita T;Shirai R;Shibata K;Okano T;Yamaguchi M;Mori Y;Hirano T;Watanabe T
通讯作者：
Watanabe T
影响因子：
15.1
作者：
Bateman, Ryon M.;Sharpe, Michael D.;Ellis, Christopher G.
通讯作者：
Ellis, Christopher G.
影响因子：
8.3
作者：
Claassen, J;Carhuapoma, JR;Mayer, SA
通讯作者：
Mayer, SA
影响因子：
3
作者：
Yang, Changjun;DeMars, Kelly M.;Candelario-Jalil, Eduardo
通讯作者：
Candelario-Jalil, Eduardo