ISX-9 Promotes KGF Secretion From MSCs to Alleviate ALI Through NGFR-ERK-TAU-Beta-Catenin Signaling Axis

The study examines the potential of isoxazole-9 (ISX-9) to enhance the therapeutic effects of mesenchymal stem cells (MSCs) in treating acute lung injury (ALI) by promoting keratinocyte growth factor (KGF) secretion. ISX-9 was identified as a potent promoter of KGF expression through the NGFR-ERK-TAU-β-catenin signaling axis. In vitro, ISX-9 increased KGF mRNA and protein levels in human and rat MSCs, with optimal effects at 5 μM after 24 hours. In a rat model of ALI, ISX-9 combined with MSCs significantly improved KGF expression, reduced inflammation, and enhanced lung repair compared to MSCs alone. The study involved 36 rats divided into 6 groups, suggesting ISX-9 could be a valuable adjunct in MSC-based therapies for ALI, although further research is needed to fully understand its interaction mechanisms with MSCs.