Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury
Tohru Minamino, Issei Komuro
Tohru Minamino, Issei Komuro
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Commentary

Regeneration of the endothelium as a novel therapeutic strategy for acute lung injury

Abstract

Acute lung injury (ALI) is characterized by the influx of protein-rich edematous fluid into the airspaces due to increased permeability of the alveolar-capillary barrier. Inflammatory mediators are thought to play a critical role in the pathogenesis of this disorder. In this issue of the JCI, Zhao et al. report that the forkhead box M1 (FoxM1) transcription factor induces endothelial regeneration and thereby restores endothelial barrier function after ALI (see the related article beginning on page 2333). Their findings raise the intriguing possibility that the promotion of endothelial regeneration may be a novel therapeutic strategy for ALI.

Authors

Tohru Minamino, Issei Komuro

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Figure 2

Regulation of FoxM1 activity and its downstream target molecules.

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Regulation of FoxM1 activity and its downstream target molecules. FoxM1 ...
FoxM1 is positively regulated by sonic hedgehog, Ras/MEK/ERK, and cyclin E/Cdk2 growth signaling pathways, among others, and inhibited by the tumor suppressor p19ARF. FoxM1 directly or indirectly modulates a number of cell cycle (replication/mitosis) regulators to promote cell proliferation and affects the signal pathways essential for organogenesis, including TGF-β signaling and VEGF signaling, thereby contributing to tissue regeneration, tumorigenesis, and organogenesis during embryonic development. Cdc25A, cell division cycle 25A; Cdc25B, cell division cycle 25B; CENP, centromere protein; Plk-1, polo-like kinase-1; p19ARF, 19-kDa alternative reading frame protein.