https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2025-0077
Announcing a new publication for
Acta Materia Medica journal. The pathogenesis of acute lung injury (ALI) and the severe form of ALI, acute respiratory distress syndrome (ARDS), is incompletely understood. The authors of this article aimed to determine the mechanism of action for non-muscle myosin heavy-chain IIA (NMMHC IIA) and the NMMHC IIA targeting compound in the context of lipopolysaccharide (LPS)-induced pulmonary endothelial barrier dysfunction associated with ALI. Endothelial-specific monoallelic knockout of NMMHC IIA alleviated ALI and reversed alterations in sphingosine-1-phosphate (S1P), a serum metabolite. Inhibition of NMMHC IIA upregulated SPHK1, a key S1P-synthesizing enzyme, and the SPHK1 transcriptional regulator, KLF2. NMMHC IIA directly interacted with FOXO1 in LPS-treated endothelial cells to promote FOXO1 nuclear translocation. Knockdown of MYH9 or FOXO1 restored barrier integrity by activating the KLF2/SPHK1 pathway. Endothelial NMMHC IIA knockdown promoted FOXO1 dephosphorylation and KLF2/SPHK1 activation
in vivo, which increased serum S1P levels; NMMHC IIA overexpression exerted opposite effects. Furthermore, DT-13, a steroidal sapogenin derived from
Liriope muscari, was confirmed to bind to NMMHC IIA via the cellular thermal shift assay (CETSA) and microscale thermophoresis (MST) assay. DT-13 attenuated LPS-induced endothelial barrier disruption by targeting NMMHC IIA and mediating the FOXO1/KLF2/SPHK1 axis. The findings described in this article elucidate a new mechanism underlying ALI pathogenesis and suggest promising therapeutic strategies.
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Jiazhi Zhang, Jiahui Tang and Huifen Ma et al. DT-13 ameliorates LPS-induced acute lung injury via targeting NMMHC IIA to modulate the FOXO1/KLF2/SPHK1 pathway.
Acta Materia Medica. 2026. Vol. 5(1):70-87. DOI: 10.15212/AMM-2025-0077