Abstract
The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin β1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin β1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin β1 signaling pathway.
Highlights
The primary and secondary soft tissue defects are a common problem in orthopedic surgery
We investigated the role of RAB37 in adipogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) and identified tissue inhibitor of matrix metalloproteinase 1 (TIMP1) as a cytokine associated with RAB37-mediated adipogenic differentiation
We first examined the expression of RAB37 during adipogenic differentiation of hADSCs using Quantitative Real-Time PCR (qRT-PCR) and western blotting
Summary
The primary and secondary soft tissue defects are a common problem in orthopedic surgery. Recent studies have demonstrated that ADSCs may assist autologous fat transplantation to repair primary and secondary soft tissue defects with significant efficacy and few complications [4]. The survival rate of autologous fat cells with ADSCs was about 70% [4]. They can secrete cytokines to improve the survival rate of autologous fat [5, 6]. HADSCs secrete a lot of cytokines that are involved in proliferation and differentiation of stem cells [11]. Regulators of cytokine secretion affect proliferation and differentiation. RAB37 is a member of RabGTPases first identified in mast cell degranulation [14].
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