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<p>Alveolar macrophage (AM) polarization plays a pivotal role in the inflammatory response during acute lung injury (ALI). As reported previously, vasodilator-stimulated phosphoprotein (VASP) may function as an anti-inflammatory agent in hepatic tissues. However, the specific role of VASP in ALI-induced macrophage polarization remains unclear. To elucidate the role of VASP in ALI, we established a lipopolysaccharide (LPS)-induced M1 polarization model of MH-S cells. RNA sequencing was performed to identify differentially expressed genes during macrophage polarization. The results revealed significant upregulation of the <i>VASP</i> gene. Subsequently, <i>VASP</i> gene knockdown in the lungs was achieved by intratracheal delivery of VASP-AAV6, and the resulting ALI symptoms and macrophage polarization were assessed. The <i>VASP</i> gene was also knocked down in MH-S cells; these cells were then stimulated with LPS for 24&#xa0;h, and polarization-related markers of macrophages were analyzed. Finally, to validate the involvement of the PKG-VASP signaling pathway, experiments were conducted with a PKG agonist (8-Br-cGMP) and inhibitor (KT5823), and the effects of modulating the PKG-VASP pathway on macrophage polarization were investigated. <i>VASP</i> knockdown notably ameliorated ALI symptoms in these mice with LPS-induced ALI. Additionally, in vitro experiments showed that the PKG-VASP signaling pathway plays a pivotal role in macrophage polarization. <i>VASP</i> knockdown protected mice from LPS-induced ALI by inhibiting M1 polarization, and its protective effects were partially mediated by the cGMP-PKG signaling pathway.</p>

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VASP Knockdown Ameliorates Lipopolysaccharide-Induced Acute Lung Injury with Inhibition of M1 Macrophage Polarization Through the cGMP-PKG Signaling Pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月5日

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  • Jiajia Tang,
  • Yiwei Ding,
  • Wei Chen,
  • Jun Shi,
  • Chunyang Zhang,
  • Xiaoyu Zhao,
  • Jiao Li,
  • Zhihai Han,
  • Xuxin Chen

摘要

Alveolar macrophage (AM) polarization plays a pivotal role in the inflammatory response during acute lung injury (ALI). As reported previously, vasodilator-stimulated phosphoprotein (VASP) may function as an anti-inflammatory agent in hepatic tissues. However, the specific role of VASP in ALI-induced macrophage polarization remains unclear. To elucidate the role of VASP in ALI, we established a lipopolysaccharide (LPS)-induced M1 polarization model of MH-S cells. RNA sequencing was performed to identify differentially expressed genes during macrophage polarization. The results revealed significant upregulation of the VASP gene. Subsequently, VASP gene knockdown in the lungs was achieved by intratracheal delivery of VASP-AAV6, and the resulting ALI symptoms and macrophage polarization were assessed. The VASP gene was also knocked down in MH-S cells; these cells were then stimulated with LPS for 24 h, and polarization-related markers of macrophages were analyzed. Finally, to validate the involvement of the PKG-VASP signaling pathway, experiments were conducted with a PKG agonist (8-Br-cGMP) and inhibitor (KT5823), and the effects of modulating the PKG-VASP pathway on macrophage polarization were investigated. VASP knockdown notably ameliorated ALI symptoms in these mice with LPS-induced ALI. Additionally, in vitro experiments showed that the PKG-VASP signaling pathway plays a pivotal role in macrophage polarization. VASP knockdown protected mice from LPS-induced ALI by inhibiting M1 polarization, and its protective effects were partially mediated by the cGMP-PKG signaling pathway.