thymosin-beta(4) has been researched along with Granulomatous-Disease--Chronic* in 1 studies
1 other study(ies) available for thymosin-beta(4) and Granulomatous-Disease--Chronic
Article | Year |
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Thymosin β4 promotes autophagy and repair via HIF-1α stabilization in chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a genetic disorder of the NADPH oxidase characterized by increased susceptibility to infections and hyperinflammation associated with defective autophagy and increased inflammasome activation. Herein, we demonstrate that thymosin β4 (Tβ4), a g-actin sequestering peptide with multiple and diverse intracellular and extracellular activities affecting inflammation, wound healing, fibrosis, and tissue regeneration, promoted in human and murine cells noncanonical autophagy, a form of autophagy associated with phagocytosis and limited inflammation via the death-associated protein kinase 1. We further show that the hypoxia inducible factor-1 (HIF-1)α was underexpressed in CGD but normalized by Tβ4 to promote autophagy and up-regulate genes involved in mucosal barrier protection. Accordingly, inflammation and granuloma formation were impaired and survival increased in CGD mice with colitis or aspergillosis upon Tβ4 treatment or HIF-1α stabilization. Thus, the promotion of endogenous pathways of inflammation resolution through HIF-1α stabilization is druggable in CGD by Tβ4. Topics: Actins; Animals; Autophagy; DNA Repair; Female; Granulomatous Disease, Chronic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice; Mice, Inbred C57BL; NADPH Oxidases; RAW 264.7 Cells; Thymosin | 2019 |