Researchers identified 3 transcription factors that are upstream of JAGGED1, an important protein for liver development and physiology, and published their findings in BMC Research Notes.
This is an important finding because in diseases like Alagille syndrome (ALGS), where there is a mutation in the gene coding for JAGGED1 in most cases, bile ducts do not develop properly. This causes a buildup of bile and leads to liver damage.
However, the molecular mechanism of JAGGED1 expression is not clear. The identification of transcription factors upstream of JAGGED1 therefore could help better understand the pathophysiology of diseases like ALGS and even allow the development of better therapies.
Read more about the pathophysiology of ALGS
In the present study, a team of researchers from Japan used an integrated bioinformatics method to search for transcription factors that regulate JAGGED1 expression. With the help of the DoRothEA database, the team identified 3 transcription factors that were predicted to be upstream of JAGGED1. These were SLUG, SRY-box 2, and early growth response 1 (EGR1).
Previously, SLUG and EGR1 were reported to be enriched in actin alpha 2-expressing portal mesenchymal cells. Moreover, portal mesenchymal cells expressing JAGGED1 had the tendency to express SLUG rather than EGR1. This, the researchers said, supports the idea that SLUG may induce the expression of JAGGED1.
“Together with the higher confidentiality of SLUG (DoRothEA level A) over EGR1 (DoRothEA level D), we concluded that SLUG was one of the most important candidate transcription factors upstream of JAGGED1,” the authors wrote. “These results add mechanistic insights into the developmental biology of how portal mesenchymal cells support biliary development in the liver.”
SLUG is a transcription factor that plays a crucial role during embryonic development. It is also expressed in adult tissues and is thought to be important for cellular function after birth.
Nishino T, Yoshihara M, Nakayama T, et al. Identifying potential regulators of JAGGED1 expression in portal mesenchymal cells. BMC Res Notes. 2022;15:172. doi:10.1186/s13104-022-06058-4