Up-Regulated Expression of Thioredoxin-Interacting Protein (TXNIP) in Mesenchymal Stem Cells Associated with Severe...

The pathogenic mechanisms of severe aplastic anemia (SAA) in children are not completely elucidated. The insufficiency of the bone marrow microenvironment, in which mesenchymal stem cells (MSCs) are an important element, can be a potential factor associated with hematopoietic impairment in SAA. In the present study, we compared bone marrow MSCs from five children with SAA and five controls. We found a higher intensity of senescence-associated β-galactosidase activity in SAA MSCs, indicating the increased senescence in these cells. Further RNA sequencing analysis identified a distinctive profile of transcriptomes in SAA MSCs. After conducting a survey of the differentially expressed genes, we found that the up-regulated expression of TXNIP may compromise the proliferative potential of MSCs and probably relate to the pathogenesis of SAA. These results were validated by qPCR. To explore the molecular mechanism involving aberrant TXNIP regulation in SAA MSCs, the expression levels of IGF-1 and IGFBP-1 were measured. A significant increase in IGFBP-1 expression was noted in SAA MSCs despite the wide range of IGF-1 expressions. Accordingly, we postulated a novel pathogenic mechanism of SAA: a compensated increase in the expression of IGF-1 in MSCs to down-regulate TXNIP expression in the face of SAA, which is offset by the up-regulated expression of IGFBP-1.