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

Int J Stem Cells. 2020 Mar 30;13(1):142-150. doi: 10.15283/ijsc19073.

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.

Keywords: Adipogenesis differentiation; Interleukin 6 (IL6); Interleukin 6 receptor (IL6R); Mesenchymal stem cells (MSCs); P38.