AP-1/C-FOS and AP-1/FRA2 differentially regulate early and late adipogenic differentiation of mesenchymal stem cells.

Autor: Bose GS; Department of Biotechnology, Savitribai Phule Pune University, Pune, India., Kalakoti G; Bioinformatics Center, Savitribai Phule Pune University, Pune, India., Kulkarni AP; Bioinformatics Center, Savitribai Phule Pune University, Pune, India., Mittal S; Department of Biotechnology, Savitribai Phule Pune University, Pune, India.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2024 Oct; Vol. 125 (10), pp. e30543. Date of Electronic Publication: 2024 Mar 05.
DOI: 10.1002/jcb.30543
Abstrakt: Obesity is defined as an abnormal accumulation of adipose tissue in the body and is a major global health problem due to increased morbidity and mortality. Adipose tissue is made up of adipocytes, which are fat-storing cells, and the differentiation of these fat cells is known as adipogenesis. Several transcription factors (TFs) such as CEBPβ, CEBPα, PPARγ, GATA, and KLF have been reported to play a key role in adipogenesis. In this study, we report one more TF AP-1, which is found to be involved in adipogenesis. Human mesenchymal stem cells  were differentiated into adipocytes, and the expression pattern of different subunits of AP-1 was examined during adipogenesis. It was observed that C-FOS was predominantly expressed at an early stage (Day 2), whereas FRA2 expression peaked at later stages (Days 6 and 8) of adipogenesis. Chromatin immunoprecipitation-sequencing analysis revealed that C-FOS binds mainly to the promoters of WNT1, miR-30a, and ANAPC7 and regulates their expression during mitotic clonal expansion. In contrast, FRA2 binds to the promoters of CIDEA, NOTCH1, ARAF, and MYLK, regulating their expression and lipid metabolism. Data obtained clearly indicate that the differential expression of C-FOS and FRA2 is crucial for different stages of adipogenesis. This also raises the possibility of considering AP-1 as a therapeutic target for treating obesity and related disorders.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: