PT  - JOURNAL ARTICLE
AU  - Giorgia Renga
AU  - Vasilis Oikonomou
AU  - Silvia Moretti
AU  - Claudia Stincardini
AU  - Marina M Bellet
AU  - Marilena Pariano
AU  - Andrea Bartoli
AU  - Stefano Brancorsini
AU  - Paolo Mosci
AU  - Andrea Finocchi
AU  - Paolo Rossi
AU  - Claudio Costantini
AU  - Enrico Garaci
AU  - Allan L Goldstein
AU  - Luigina Romani
TI  - Thymosin β4 promotes autophagy and repair via HIF-1α stabilization in chronic granulomatous disease
AID  - 10.26508/lsa.201900432
DP  - 2019 Dec 01
TA  - Life Science Alliance
PG  - e201900432
VI  - 2
IP  - 6
4099  - https://www.life-science-alliance.org/content/2/6/e201900432.short
4100  - https://www.life-science-alliance.org/content/2/6/e201900432.full
SO  - Life Sci. Alliance2019 Dec 01; 2
AB  - 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.