IL6 Receptor Facilitates Adipogenesis Differentiation of Human Mesenchymal Stem Cells through Activating P38 Pathway

Abstract

Background and Objectives: Mesenchymal stem cells (MSCs) have the multipotent capacity to differentiate into multiple tissue lineages as well as to self-renew, which is the main origin of adipocytes. IL6/IL6R pathway exerts a significant role in tissue regeneration and cell differentiation. Whereas, the underlying mechanism between IL6/IL6R pathway and MSCs adipogenesis differentiation remains elusive. Methods: MSCs from healthy donors were cultured in adipogenesis differentiation medium for 0∼14 days, during which their adipogenesis differentiation degree was evaluated by Oil Red O staining. The expression of IL6R was detected in MSCs during adipogenesis differentiation. Knockdown and overexpression of IL6R were respectively performed using siRNA and lentivirus to investigate its effect on MSCs adipogenesis differentiation. The adipogenesis marker genes expression and MAPK pathway activation were detected by Western blotting. The role of P38 pathway in the adipogenesis differentiation of MSCs was determined using the specific inhibitor SB203580. Results: The expression of IL6 and IL6R increased during adipogenesis differentiation in MSCs, which were positively correlated with Oil Red O quantification result. Knockdown and overexpression experiments demonstrated a positive correlation between the expressions of IL6R and MSCs adipogenesis differentiation, accompanied by same trend of P38 phosphorylation. Besides, the specific P38 inhibitor SB203580 markedly inhibited the adipogenesis differentiation potential of MSCs. Conclusions: This study reveals IL6R facilitates the adiogenesis differentiation of MSCs via activating P38 pathway.

Comparative analysis of gene expression profiles in differentiated subcutaneous adipocytes between Jiaxing Black and Large White pigs

“…Owing to the opposing roles described for the MAPK pathway, one hypothesis states that the activation of MAPK can have different effects depending on the stage of differentiation. This hypothesis is in agreement with the fact that the differentiation process of 3 T3-L1 adipocytes requires a specific proliferative step (called mitotic clonal expansion, MCE) at the beginning [38,40]. In addition, p38 MAPK activity was significantly higher in preadipocytes than in adipocytes [39], again suggesting that p38 MAPK activity has to be regulated in a timely manner during adipocyte differentiation.…”

Comparative analysis of gene expression profiles in differentiated subcutaneous adipocytes between Jiaxing Black and Large White Pigs

“…Therefore, the results of this study indicate that the MAPK signaling pathway may be important for mediating subcutaneous adipogenesis in Jiaxing Black pigs. Considering that ERK and p38 are two main kinases in the MAPK pathway, and opposite results were observed for the regulatory functions of ERK and p38 during adipocyte differentiation [35][36][37], we further compared the activation of p38/ERK in subcutaneous adipose tissue of the two pig breeds. We found that there was practically no p38 phosphorylation in LW pigs, which contrasted with high abundance of phosphorylated p38 in JX pig adipocytes.…”

Endothelial progenitor cells promote osteogenic differentiation in co-cultured with mesenchymal stem cells via the MAPK-dependent pathway

“…Consistently, ALP levels and calcium nodule formation were both suppressed by p38 silencing (Figure 6E [28]. The ability of MSCs to differentiate into multiple lineages is controlled by various inhibitors and stimulators, which have been studied by in vivo or in vitro [29,30]. Enhanced MSCs osteogenic differentiation can be achieved by various methods, such as electrical stimulation, chemical supplements, and co-culturing with assisting cells [31,32].…”