Tissue Inhibitor of Metalloprotease-1 (TIMP-1) Regulates Adipogenesis of Adipose-derived Stem Cells (ASCs) via the Wnt Signaling Pathway in an MMP-independent Manner

Abstract

Tissue inhibitor of metalloprotease-1 (TIMP-1) is a tissue inhibitor of matrix metalloproteinases (MMPs). It however exerts multiple effects on biological processes, such as cell growth, proliferation, differentiation and apoptosis, in an MMP-independent manner. This study aimed to examine the role of TIMP-1 in adipogenesis of adipose-derived stem cells (ASCs) and the underlying mechanism. We knocked down the TIMP-1 gene in ASCs through lentiviral vectors encoding TIMP-1 small interfering RNA (siRNA), and then found that the knockdown of TIMP-1 in ASCs promoted the adipogenic differentiation of stem cells and inhibited the Wnt/β-catenin signaling pathway in ASCs. We also noted that mutant TIMP-1 without the inhibitory activity on MMPs promoted the activation of Wnt/β-catenin pathway as well as the recombinant wild type TIMP-1 did, which indicated that the effect of TIMP-1 on Wnt/β-catenin pathway was MMP-independent. Our study suggested that TIMP-1 negatively regulated the adipogenesis of ASCs via the Wnt/β-catenin signaling pathway in an MMP-independent manner.

Keywords

tissue inhibitor of metalloproteinase 1 / adipose-derived stem cells / adipogenesis / Wnt/β-catenin pathway

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