Identification of a small molecule preventing BMSC senescence in vitro by improving intracellular homeostasis via ANXA7 and Hmbox1

Abstract

Recently, small chemical molecules have been proved to be ideal and promising interventions for bone marrow-derived mesenchymal stem cell (BMSC)-based tissue regeneration therapies. In this study, we discovered the huge anti-aging potential of a bioactive small molecule, 6-amino-3,4-dihydro-2H-3-hydroxymethyl-1,4-benzoxazine (ABO), which can suppress a series of senescent phenotypes, enhancing the proliferation and differentiation capacities in cultured rat BMSCs. We further illustrated that those beneficial effects were attributed to an improvement in cellular homeostasis, from the intracellular degradation system to cytoskeleton organization. ABO could enhance autophagy and reduce intracellular oxidative stress, by facilitating lysosomal degradation. The direct target protein of ABO, ANXA7, was elevated and proved essential for autophagy induction and lysosomal protection against Baf-A1 upon ABO treatment. Hmbox1 was another critical protein elevated by ABO, and probably downstream ANXA7. Intriguingly, the subcellular distribution of Hmbox1 largely overlapped with cytoskeletal microfilaments and this might lead to a microfilament reorganization. ABO could decrease the level of Caveolin-1, indicating a remodeling of the F-actin assembly and has attracted our interest to investigate the interaction between Hmbox1, Caveolin-1 and ANXA7 in microfilament formation at the cell membrane in a future study.