Work

Faecalibaculum rodentium protects HSCs from IR-induced apoptosis via suppression of nuclear PKM2-enhanced p53 transcriptional activity

Year: 2023

Type: preprint

Abstract: It has been shown that under various conditions, such as aging, the gut flora contributes to modulating the status and functions of hematopoietic stem cells (HSCs). However, which species/strains of probiotics and the underlying mechanisms involved in controlling HSC function remain obscure, especially under irradiation conditions. In this study, we found that an antibiotic cocktail caused STAT3 localization in the mitochondria of epithelial cells along with a decrease in the abundance of F. rodentium. Feeding mice with F. rodentium and its metabolite butyrate prolonged the survival of irradiated mice. In a further study, we found that the administration of butyrate sustained nuclear PKM2 expression, attenuating p53-induced apoptosis. These results suggested that in response to irradiation, a reduced abundance of F. rodentium led to decreased butyrate content, thereby promoting PKM2 nuclear translocation, which subsequently enhanced p53 transcriptional activity.

Source: Research Square

DOI: 10.21203/rs.3.rs-3723122/v1