The latest research shows that the new small molecule compound Me6TREN can promote the regeneration of intestinal stem cells after radiation, and is expected to become a candidate drug for the treatment of acute intestinal radiation sickness.
On August 13, 2020, the international academic journal Theranostics published the latest research results “Me6TREN targets β-catenin signaling to stimulate intestinal stem cell regeneration after radiation” from the Academy of Military Medicine of the Academy of Military Sciences and the South China Stem Cell and Regenerative Medicine Research Center. The study found that the new small molecule compound Me6TREN (Me6) can regulate the regeneration of intestinal stem cells by activating the ERK/AKT-β-catenin signaling pathway, thereby significantly improving the survival of mouse model with intestinal radiation sickness.
Acute gastrointestinal syndrome (AGS) is one of the most serious clinical manifestations after exposure to high doses of radiation. However, there is currently a lack of FDA-approved drugs that can be used to reduce the damage of intestinal tissue exposed to radiation and accelerate the regeneration of injured epithelium. Therefore, promoting the regeneration and repair of damaged tissues based on stem cell technology is one of the key research directions of the research team.
In early trials, the team of researchers discovered through the stem cell technology platform that the new small molecule compound Me6 has the function of mobilizing hematopoietic stem/progenitor cells and endothelial progenitor cells in the bone marrow, and can promote angiogenesis in the ischemic lower limbs.
In this study, the researchers found that the systemic administration of Me6 significantly improved the regeneration of intestinal stem cells and crypt cells, and increased the survival rate of mice after high-dose radiation. Me6 significantly activated the expression of intestinal stem cell genes and proliferation promoting genes, such as Ascl2, Lgr5, Myc and CyclinD1, so they speculated that the compound may have the effect of promoting the regeneration and repair of radiation-damaged tissues. Through further research, it is found that Me6 regulates the regeneration function of intestinal stem cells by activating the ERK/AKT-β-catenin signaling pathway. It is worth noting that the researchers found that Me6 has no significant effect on the growth of tumor tissue formed by HCT116 cells in vivo, suggesting that the compound has potential clinical application prospects.
Reference
1 Wang S, et al. Me6TREN targets β-catenin signaling to stimulate intestinal stem cell regeneration after radiation.Theranostics，2020; 10(22): 10171-10185.