The splicing factor SRSF1 stabilizes the mRNA of TSLP to enhance acute lung injury

Fu Chunlai; Hu Yahui; Liu Jiean; Yang You

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The splicing factor SRSF1 stabilizes the mRNA of TSLP to enhance acute lung injury

机译：剪接因子SRSF1稳定TSLP的mRNA以增强急性肺损伤

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Acute lung injury (ALI) is a severe disease with a high rate of morbidity and mortality, characterized by excessive and uncontrolled inflammatory response in lung. Recent studies demonstrated that serine arginine-rich splicing factor 1 (SRSF1) is involved in inflammation. However, whether SRSF1 modulates ALI remains to be determined. In this study, we established an ALI mouse model that induced by lipopolysaccharide (LPS), with or without the treatment of SRSF1 antibody. Our result showed that SRSF1 expression was elevated in LPS-induced ALI. Importantly, treatment with SRSF1 antibody notably ameliorated ALI in mice, as determined by reduction in lung W/D ratios, histopathological changes, lung inflammation and TSLP expression. Besides, exposure of human alveolar epithelial A549 cells to LPS enhanced the expression of both SRSF1 and TSLP, while knockdown or overexpression of SRSF1 significantly lowered or upregulated the expression of TSLP induced by LPS. Interestingly, the expression of SRSF1 and TSLP showed a positive correlation in normal human lung tissues. Mechanistically, we found that SRSF1 directly bound with the mRNA of TSLP and may exert its function by stabilizing the mRNA of TSLP in LPS-induced ALI. Therefore, our results indicated that SRSF1 may be an important contributor in lung inflammation of LPS-induced ALI and SRSF1 signaling blocking may serve as a potential treatment of ALI.

机译：急性肺损伤（ALI）是一种发病率和死亡率都很高的严重疾病，其特点是肺部炎症反应过度且不受控制。最近的研究表明，富含丝氨酸精氨酸的剪接因子1（SRSF1）与炎症有关。然而，SRSF1是否调节ALI仍有待确定。在本研究中，我们建立了一个由脂多糖（LPS）诱导的ALI小鼠模型，无论是否治疗SRSF1抗体。我们的结果表明，在LPS诱导的ALI中，SRSF1的表达升高。重要的是，SRSF1抗体治疗可显著改善小鼠的ALI，这可通过降低肺W/D比、组织病理学变化、肺部炎症和TSLP表达来确定。此外，人肺泡上皮A549细胞暴露于LPS可增强SRSF1和TSLP的表达，而SRSF1的敲除或过度表达可显著降低或上调LPS诱导的TSLP的表达。有趣的是，SRSF1和TSLP在正常人肺组织中的表达呈正相关。在机制上，我们发现SRSF1直接与TSLP的mRNA结合，并可能通过稳定LPS诱导的ALI中TSLP的mRNA发挥其功能。因此，我们的结果表明，SRSF1可能是LPS诱导的ALI肺部炎症的一个重要因素，SRSF1信号阻断可能是ALI的一种潜在治疗方法。

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来源
《Cellular immunology》 |2021年第1期|共7页
作者
Fu Chunlai; Hu Yahui; Liu Jiean; Yang You;
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作者单位

Southern Med Univ Affiliated Dongguan Peoples Hosp Dept Emergency Intens Care Unit Dongguan;

Southern Theatre Command PLA Gen Hosp Dept Geriatr Resp Med Guangzhou Guangdong Peoples R China;

Southern Med Univ Affiliated Dongguan Peoples Hosp Dept Emergency Intens Care Unit Dongguan;

Southern Med Univ Affiliated Dongguan People Hosp Dept Radiol Dongguan Guangdong Peoples R;

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正文语种 eng
中图分类细胞生物学;
关键词
SRSF1; TSLP; Acute lung injury; Inflammatory response;

机译：SRSF1;TSLP;急性肺损伤;炎症反应;

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The splicing factor SRSF1 stabilizes the mRNA of TSLP to enhance acute lung injury

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