Abstract
BackgroundTransforming growth factor-β1 (TGF-β1) induces the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle cells. Lipid rafts are cholesterol-rich microdomains in cell membranes that reportedly play a key role in receptor-mediated signal transduction and cellular responses. In order to clarify whether lipid rafts are involved in TGF-β1-induced differentiation of hASCs into smooth muscle cells, we analyzed the lipid raft proteome of hASCs.Methods and ResultsPretreatment of hASCs with the lipid raft disruptor methyl-β-cyclodextrin abrogated TGF-β1-induced expression of α-smooth muscle actin, a smooth muscle cell marker, suggesting a pivotal role of lipid rafts in TGF-β1-induced differentiation of hASCs to smooth muscle cells. Sucrose density gradient centrifugation along with a shotgun proteomic strategy using liquid chromatography-tandem mass spectrometry identified 1002 individual proteins as the lipid raft proteome, and 242 of these were induced by TGF-β1 treatment. ADAM12, a disintegrin and metalloproteases family member, was identified as the most highly up-regulated protein in response to TGF-β1 treatment. TGF-β1 treatment of hASCs stimulated the production of both ADAM12 protein and mRNA. Silencing of endogenous ADAM12 expression using lentiviral small hairpin RNA or small interfering RNA abrogated the TGF-β1-induced differentiation of hASCs into smooth muscle cells.ConclusionsThese results suggest a pivotal role for lipid raft-associated ADAM12 in the TGF-β1-induced differentiation of hASCs into smooth muscle cells.
Highlights
Mesenchymal stem cells (MSCs) have self-renewal ability, longterm viability, and the potential to differentiate into diverse cells types, including adipogenic, osteogenic, chondrogenic, and myogenic lineages [1,2,3,4]
These results suggest a pivotal role for lipid raft-associated ADAM12 in the Transforming growth factor-b1 (TGF-b1)-induced differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle cells
We previously demonstrated that the expression of Smooth muscle cells (SMCs)-specific markers is up-regulated in human adipose tissue-derived mesenchymal stem cells by treatment with TGF-b1 and sphingosylphosphorylcholine [18,19], suggesting a potential role for hASCs as SMC progenitors
Summary
Mesenchymal stem cells (MSCs) have self-renewal ability, longterm viability, and the potential to differentiate into diverse cells types, including adipogenic, osteogenic, chondrogenic, and myogenic lineages [1,2,3,4]. Smooth muscle cells (SMCs) have been implicated in vascular development as well as a variety of cardiovascular diseases, including hypertension and atherosclerosis [8,9]. Transforming growth factor-b (TGF-b) family cytokines have been implicated in a variety of cellular responses, such as proliferation, differentiation, and apoptosis [10,11]. We previously demonstrated that the expression of SMC-specific markers is up-regulated in human adipose tissue-derived mesenchymal stem cells (hASCs) by treatment with TGF-b1 and sphingosylphosphorylcholine [18,19], suggesting a potential role for hASCs as SMC progenitors. Transforming growth factor-b1 (TGF-b1) induces the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle cells. Lipid rafts are cholesterol-rich microdomains in cell membranes that reportedly play a key role in receptor-mediated signal transduction and cellular responses. In order to clarify whether lipid rafts are involved in TGF-b1-induced differentiation of hASCs into smooth muscle cells, we analyzed the lipid raft proteome of hASCs
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