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Proteomic Analysis of Extracellular HMGB1 Identifies Binding Partners and Exposes Its Potential Role in Airway Epithelial Cell Homeostasis
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2017-11-14 00:00:00 , DOI: 10.1021/acs.jproteome.7b00212 Sharon L. Wong 1 , Joyce To 2 , Jerran Santos 2 , Venkata Sita Rama Raju Allam 1 , John P. Dalton 2, 3 , Steven P. Djordjevic 4 , Sheila Donnelly 2 , Matthew P. Padula 2, 4 , Maria B. Sukkar 1
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2017-11-14 00:00:00 , DOI: 10.1021/acs.jproteome.7b00212 Sharon L. Wong 1 , Joyce To 2 , Jerran Santos 2 , Venkata Sita Rama Raju Allam 1 , John P. Dalton 2, 3 , Steven P. Djordjevic 4 , Sheila Donnelly 2 , Matthew P. Padula 2, 4 , Maria B. Sukkar 1
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The release of damage-associated molecular patterns (DAMPs) by airway epithelial cells is believed to play a crucial role in the initiation and development of chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Intriguingly, the classic DAMP high-mobility group box-1 (HMGB1) is detected in the culture supernatant of airway epithelial cells under basal conditions, indicating a role for HMGB1 in the regulation of epithelial cellular and immune homeostasis. To gain contextual insight into the potential role of HMGB1 in airway epithelial cell homeostasis, we used the orthogonal and complementary methods of high-resolution clear native electrophoresis, immunoprecipitation, and pull-downs coupled to liquid chromatography–tandem mass spectrometry (LC–MS/MS) to profile HMGB1 and its binding partners in the culture supernatant of unstimulated airway epithelial cells. We found that HMGB1 presents exclusively as a protein complex under basal conditions. Moreover, protein network analysis performed on 185 binding proteins revealed 14 that directly associate with HMGB1: amyloid precursor protein, F-actin-capping protein subunit alpha-1 (CAPZA1), glyceraldehyde-3 phosphate dehydrogenase (GAPDH), ubiquitin, several members of the heat shock protein family (HSPA8, HSP90B1, HSP90AA1), XRCC5 and XRCC6, high mobility group A1 (HMGA1), histone 3 (H3F3B), the FACT (facilitates chromatin transcription) complex constituents SUPT1H and SSRP1, and heterogeneous ribonucleoprotein K (HNRNPK). These studies provide a new understanding of the extracellular functions of HMGB1 in cellular and immune homeostasis at the airway mucosal surface and could have implications for therapeutic targeting.
中文翻译：
胞外HMGB1的蛋白质组学分析确定了结合伴侣，并揭示了其在气道上皮细胞动态平衡中的潜在作用
据信，气道上皮细胞释放与损伤相关的分子模式（DAMP）在哮喘和慢性阻塞性肺病（COPD）等慢性气道疾病的发作和发展中起着至关重要的作用。有趣的是，在基础条件下在气道上皮细胞的培养上清液中检测到经典的DAMP高迁移率族box-1（HMGB1），这表明HMGB1在调节上皮细胞和免疫稳态中的作用。为了从背景上了解HMGB1在气道上皮细胞动态平衡中的潜在作用，我们使用了高分辨率的清晰天然电泳，免疫沉淀，并通过液相色谱-串联质谱（LC-MS / MS）进行下拉，以分析未刺激的气道上皮细胞培养上清液中的HMGB1及其结合伴侣。我们发现，HMGB1仅在基础条件下呈现为蛋白质复合物。此外，对185种结合蛋白进行的蛋白网络分析表明，有14种蛋白直接与HMGB1相关：淀粉样蛋白前体蛋白，F-肌动蛋白封端蛋白亚基α-1（CAPZA1），甘油醛3磷酸脱氢酶（GAPDH），遍在蛋白，热休克蛋白家族（HSPA8，HSP90B1，HSP90AA1），XRCC5和XRCC6，高迁移率A1组（HMGA1），组蛋白3（H3F3B），FACT（促进染色质转录）复杂成分SUPT1H和SSRP1以及异源核糖核酸K ）。
更新日期：2017-11-15
中文翻译：
胞外HMGB1的蛋白质组学分析确定了结合伴侣，并揭示了其在气道上皮细胞动态平衡中的潜在作用
据信，气道上皮细胞释放与损伤相关的分子模式（DAMP）在哮喘和慢性阻塞性肺病（COPD）等慢性气道疾病的发作和发展中起着至关重要的作用。有趣的是，在基础条件下在气道上皮细胞的培养上清液中检测到经典的DAMP高迁移率族box-1（HMGB1），这表明HMGB1在调节上皮细胞和免疫稳态中的作用。为了从背景上了解HMGB1在气道上皮细胞动态平衡中的潜在作用，我们使用了高分辨率的清晰天然电泳，免疫沉淀，并通过液相色谱-串联质谱（LC-MS / MS）进行下拉，以分析未刺激的气道上皮细胞培养上清液中的HMGB1及其结合伴侣。我们发现，HMGB1仅在基础条件下呈现为蛋白质复合物。此外，对185种结合蛋白进行的蛋白网络分析表明，有14种蛋白直接与HMGB1相关：淀粉样蛋白前体蛋白，F-肌动蛋白封端蛋白亚基α-1（CAPZA1），甘油醛3磷酸脱氢酶（GAPDH），遍在蛋白，热休克蛋白家族（HSPA8，HSP90B1，HSP90AA1），XRCC5和XRCC6，高迁移率A1组（HMGA1），组蛋白3（H3F3B），FACT（促进染色质转录）复杂成分SUPT1H和SSRP1以及异源核糖核酸K ）。
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