Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions.
Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions.
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DOI：
10.1038/s41598-022-11045-7
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发表时间：
2022-04-29
影响因子：
4.6
通讯作者：
Vidal Melo MF
中科院分区：
文献类型：
--
作者：
Rashid A;Zeng C;Motta-Ribeiro G;Dillon ST;Libermann TA;Lessa MA;Bagchi A;Hutchinson J;Vidal Melo MF
肺不张是一种常见的临床病症，但对其对肺损伤的生物学影响的了解有限且存在争议。我们评估了肺不张与正常通气肺组织的区域蛋白质组学，以检验免疫和肺泡毛细血管屏障功能因纯粹的肺不张而受到损害以及因额外的全身炎症（脂多糖，LPS）而失调的假设。在没有 LPS 的情况下，肺不张与通气肺中的 130 种蛋白质的丰度存在差异，其中大多数 (n = 126) 丰度较低，并且免疫、内皮和上皮功能以及 Hippo 信号通路中的过程呈负富集。相反，暴露于 LPS 的肺不张产生了 174 种差异丰富的蛋白质，其中大部分（n = 108）增加，包括急性肺损伤标志物 RAGE 和趋化因子 CCL5。功能分析表明，LPS 增强了白细胞过程，并负富集了细胞-基质粘附和细胞连接组装。此外，无论LPS如何，在粘附糖蛋白THBS1减少的肺不张中，细胞外基质组织和TGF-β信号传导呈负富集。转录组学和蛋白质组学子集的一致性揭示了白细胞相关基因-蛋白质对和过程的重叠。总之，仅肺不张的蛋白质组学表明免疫反应减少，而免疫反应会转化为脂多糖反应增加。无论脂多糖如何，肺不张中肺泡毛细血管屏障功能相关的蛋白质组学反应都会下调。特定的蛋白质组学特征表明了肺不张相关肺损伤的生物机制和治疗靶点。
Atelectasis is a frequent clinical condition, yet knowledge is limited and controversial on its biological contribution towards lung injury. We assessed the regional proteomics of atelectatic versus normally-aerated lung tissue to test the hypothesis that immune and alveolar-capillary barrier functions are compromised by purely atelectasis and dysregulated by additional systemic inflammation (lipopolysaccharide, LPS). Without LPS, 130 proteins were differentially abundant in atelectasis versus aerated lung, mostly (n = 126) with less abundance together with negatively enriched processes in immune, endothelial and epithelial function, and Hippo signaling pathway. Instead, LPS-exposed atelectasis produced 174 differentially abundant proteins, mostly (n = 108) increased including acute lung injury marker RAGE and chemokine CCL5. Functional analysis indicated enhanced leukocyte processes and negatively enriched cell–matrix adhesion and cell junction assembly with LPS. Additionally, extracellular matrix organization and TGF-β signaling were negatively enriched in atelectasis with decreased adhesive glycoprotein THBS1 regardless of LPS. Concordance of a subset of transcriptomics and proteomics revealed overlap of leukocyte-related gene-protein pairs and processes. Together, proteomics of exclusively atelectasis indicates decreased immune response, which converts into an increased response with LPS. Alveolar-capillary barrier function-related proteomics response is down-regulated in atelectasis irrespective of LPS. Specific proteomics signatures suggest biological mechanistic and therapeutic targets for atelectasis-associated lung injury.
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作者：
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通讯作者：
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