Relationship Between Expression Levels of Rps6kb1 and Gli1 With Dyrk1b During Adipogenesis of Adscs in the Presence and Absence of R102c Mutation in Dyrk1b Gene

Background and aim: metabolic syndrome is increasing as a worldwide health problem, including iran. the missense mutation of the dyrk1b gene r102c in an iranian population has been shown to be correlated to a rare autosomal-dominant form of the metabolic syndrome. rate of adipogenesis is increased in the presence of the mutated gene which can be through the interactions with shh pathway although the details of dyrk1b interactions with other components of adipogenic pathways is not completely understood. gli1 is a transcription factor and is the final effector of shh pathway. gene rps6kb1 encodes a kinase called s6k and plays a role at early stages of adipogenesis. c/ebpα and pparγ are two major regulators of adipogenesis and their expression levels increased during this process. in the current study we assessed the expression levels of dyrk1b, gli1, rps6kb1 , c/ebpα and pparγ in the day1, 5 and 10 after adipogenesis induction . methods: the adscs were obtained from two groups of donors, affected with r102c mutation in dyrk1b gene and non-affected ones, characterized using flow cytometry. the obtained adscs were cultured and differentiated into adipocytes. adipogenic differentiation was confirmed with oil red o staining. after total rna extraction and cdna synthesis, the gene expression levels were evaluated by real-time pcr. the results were analyzed by two-way anova test using graph pad prism. results: after adipogenesis induction the expression of c/ebpα and pparγ in both groups increased, also they were higher in the mutated group significantly. dyrk1b expression increased during the day1 and 5 and decreased at day10, not analytically significant. rps6kb1 increased in the day1 and 5 and decreased at day10; gli1 expression decreased in all days. although changes of rps6kb1 and gli1 were significant within each group, it wasn’t between the groups. conclusion: the r102c mutation of dyrk1b can increase adipogenesis. during adipogenesis, shh pathway activity is decreased (according to gli1 descending levels). rps6kb1 ascending levels in day1 and 5 is correlated with early stages of adipogenesis. since the changes of rps6kb1 and gli1 aren’t significant between groups, different rates of adipogenesis in the case r102c mutation cannot be related to gli1 or s6k directly.