研究动态
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维生素 D 结合蛋白:老年 COVID-19 急性肺损伤的潜在因素。

Vitamin D Binding Protein: A Potential Factor in Geriatric COVID-19 Acute Lung Injury.

发表日期:2024
作者: Hongjuan Jiang, Xiangyu Chi, Yanhong Sun, Hongwen Li
来源: Disease Models & Mechanisms

摘要:

此前的研究表明,维生素D结合蛋白(VDBP)是一种独立的多功能蛋白,在急性炎症和组织损伤中发挥着至关重要的作用。然而,其在 2019 年冠状病毒病 (COVID-19) 引起的急性肺损伤 (ALI) 中的作用尚不清楚,也缺乏研究。本研究拟探讨合并ALI与不合并ALI的COVID-19患者血清VDBP水平的差异,并通过细胞模型进一步探讨VDBP在ALI炎症反应中的作用。收集自COVID-19患者的血清,检测血清VDBP浓度。构建VDBP基因沉默质粒并转染人肺泡上皮A549细胞。脂多糖(LPS)干预72小时后,检测炎症因子白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α),并采用细胞计数试剂盒8(CCK-8)检测检测细胞活力。采用流式细胞术检测细胞凋亡情况。COVID-19合并ALI时血清VDBP浓度显着升高(P < 0.05)。相关分析显示,血清VDBP与白细胞(r=0.329,P=0.002)、C反应蛋白(r=0.470,P<0.001)、血清淀粉样蛋白A(r=0.900,P<0.001)、降钙素原(r=0.470,P<0.001)呈正相关。 0.670,P < 0.001) 和白细胞介素 6 (r = 0.452,P < 0.001)。同时,Logistic回归分析显示,血清VDBP升高是COVID-19患者发生ALI的独立危险因素(OR 1.003 95% CI 1.001-1.006,P = 0.002)。人肺泡上皮A549细胞中,LPS干预后,VDBP基因沉默组炎症因子IL-1β和TNF-A较阴性对照组(NC)组显着降低(P < 0.05)。 VDBP基因沉默组细胞活力较NC组显着升高,细胞凋亡率显着降低(P < 0.05)。在COVID-19患者中,急性肺损伤可能导致血清VDBP浓度升高。 VDBP 在促进炎症反应和支气管上皮细胞凋亡中发挥着重要作用。© 2024 Jiang et al.
Previous research indicated that vitamin D binding protein (VDBP) is an independent multifunctional protein that plays a vital role in acute inflammatory and tissue damage. However, its role in acute lung injury (ALI) due to coronavirus disease 2019 (COVID-19) is unclear, and studies are lacking. This study intends to investigate the difference in serum VDBP levels in COVID-19 patients with ALI or without ALI and further explore the role of VDBP in the inflammatory response of ALI through cellular models.The serum was collected from COVID-19 patients, and the concentration of serum VDBP was detected. Construct a VDBP gene-silencing plasmid and transfect it into human alveolar epithelial A549 cells. After 72 hours of lipopolysaccharide (LPS) intervention, The inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected, and cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis.The serum concentration of VDBP was significantly higher in COVID-19 with ALI (P < 0.05). Correlation analysis indicated serum VDBP positively correlated with leukocyte (r=0.329, P = 0.002), c-reaction protein (r = 0.470, P < 0.001), serum amyloid A (r = 0.900, P < 0.001), procalcitonin (r = 0.670, P < 0.001), and interleukin 6 (r = 0.452, P < 0.001). Simultaneously, the logistic regression analysis showed that increased serum VDBP was an independent risk factor for ALI in COVID-19 patients (OR 1.003 95% CI 1.001-1.006, P = 0.002). In human alveolar epithelial A549 cells, after LPS intervention, the inflammatory factor IL-1β and TNF-A significantly reduced in the VDBP gene silencing group compared to the negative control (NC) group (P < 0.05). The cell viability of the VDBP gene silencing group was significantly increased compared to the NC group, and the cell apoptosis rate was significantly reduced (P < 0.05).In COVID-19 patients, acute lung injury may lead to increased serum concentration of VDBP. VDBP plays a vital role in promoting inflammatory response and apoptosis of bronchial epithelial cells.© 2024 Jiang et al.