Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy.
Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy.
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DOI：
10.3390/life11080827
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发表时间：
2021-08-13
期刊：
影响因子：
--
通讯作者：
Hathout Y
中科院分区：
文献类型：
--
作者：
Ogundele M;Zhang JS;Goswami MV;Barbieri ML;Dang UJ;Novak JS;Hoffman EP;Nagaraju K;Cinrg-Dnhs Investigators;Hathout Y
杜氏肌营养不良症（DMD）是一种进行性肌肉疾病，涉及复杂的骨骼肌发病机制。其发病机制是由于肌营养不良蛋白表达缺乏而导致肌膜不稳定，导致Ca2+内流、肌纤维凋亡、炎症、肌肉坏死和纤维化。我们的实验室最近使用了两种高通量多重技术（例如 SomaScan® 适体测定和串联质量标签 (TMT) 方法），并鉴定了一系列与不同病理生化途径相关的血清蛋白生物标志物。在这项研究中，我们重点验证三种促炎趋化因子（CCL2、CXCL10 和 CCL18）的循环水平，这三种趋化因子被认为参与肌肉发病机制的早期阶段。我们使用高度特异性和可重复的 MSD ELISA 检测，并检查了这些趋化因子与 DMD 发病机制、年龄、疾病严重程度和对糖皮质激素治疗的反应的关联。正如预期的那样，我们证实，相对于年龄匹配的健康对照，DMD 患者的血清和肌肉样本中这三种趋化因子显着升高（p 值 < 0.05，肌肉样本中 CCL18 没有显着改变）。与对照组进行单向方差分析时，这三种趋化因子在贝克型肌营养不良 (BMD) 患者（一种较温和的肌营养不良症）中并未显着升高，但在年龄匹配的 DMD 组中仍然显着升高（p < 0.05）。在 DMD 患者中，CCL2 和 CCL18 但不包括 CXCL10 随着年龄的增长而下降，而在 BMD 和对照组中，所有三种趋化因子都随着年龄的增长而保持不变。在 DMD 组中，只有 CCL2 与爬四级台阶的时间显着相关（r = 0.48，p = 0.038），并且在 BMD 组中与患者报告的结果接近显着相关（r = 0.39，p = 0.058）。此外，与野生型小鼠模型相比，DMD mdx 小鼠模型的血清中发现 CCL2 升高。这项研究表明，CCL2 可能是后续研究的合适候选生物标志物，以证明其在 DMD 中的生理意义和临床实用性。
Duchenne muscular dystrophy (DMD) is a progressive muscle disease involving complex skeletal muscle pathogenesis. The pathogenesis is triggered by sarcolemma instability due to the lack of dystrophin protein expression, leading to Ca2+ influx, muscle fiber apoptosis, inflammation, muscle necrosis, and fibrosis. Our lab recently used two high-throughput multiplexing techniques (e.g., SomaScan® aptamer assay and tandem mass tag-(TMT) approach) and identified a series of serum protein biomarkers tied to different pathobiochemical pathways. In this study, we focused on validating the circulating levels of three proinflammatory chemokines (CCL2, CXCL10, and CCL18) that are believed to be involved in an early stage of muscle pathogenesis. We used highly specific and reproducible MSD ELISA assays and examined the association of these chemokines with DMD pathogenesis, age, disease severity, and response to glucocorticoid treatment. As expected, we confirmed that these three chemokines were significantly elevated in serum and muscle samples of DMD patients relative to age-matched healthy controls (p-value < 0.05, CCL18 was not significantly altered in muscle samples). These three chemokines were not significantly elevated in Becker muscular dystrophy (BMD) patients, a milder form of dystrophinopathy, when compared in a one-way ANOVA to a control group but remained significantly elevated in the age-matched DMD group (p < 0.05). CCL2 and CCL18 but not CXCL10 declined with age in DMD patients, whereas all three chemokines remained unchanged with age in BMD and controls. Only CCL2 showed significant association with time to climb four steps in the DMD group (r = 0.48, p = 0.038) and neared significant association with patients’ reported outcome in the BMD group (r = 0.39, p = 0.058). Furthermore, CCL2 was found to be elevated in a serum of the mdx mouse model of DMD, relative to wild-type mouse model. This study suggests that CCL2 might be a suitable candidate biomarker for follow-up studies to demonstrate its physiological significance and clinical utility in DMD.
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影响因子：
3.4
作者：
De Paepe, Boel;Creus, Kim K.;De Bleecker, Jan L.
通讯作者：
De Bleecker, Jan L.
影响因子：
4.8
作者：
Pescatori, Mario;Broccolini, Aldobrando;Ricci, Enzo
通讯作者：
Ricci, Enzo
影响因子：
3.6
作者：
Kranig, Simon Alexander;Tschada, Raphaela;Hudalla, Hannes
通讯作者：
Hudalla, Hannes
影响因子：
3.4
作者：
McDonald, Craig M.;Henricson, Erik K.;Abresch, R. Ted;Han, Jay J.;Escolar, Diana M.;Florence, Julaine M.;Duong, Tina;Arrieta, Adrienne;Clemens, Paula R.;Hoffman, Eric P.;Cnaan, Avital
通讯作者：
Cnaan, Avital
DOI：
10.1073/pnas.1507719112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Hathout Y;Brody E;Clemens PR;Cripe L;DeLisle RK;Furlong P;Gordish-Dressman H;Hache L;Henricson E;Hoffman EP;Kobayashi YM;Lorts A;Mah JK;McDonald C;Mehler B;Nelson S;Nikrad M;Singer B;Steele F;Sterling D;Sweeney HL;Williams S;Gold L
通讯作者：
Gold L