Label-free quantitative proteomics identifies transforming growth factor β1 (TGF-β1) as an inhibitor of adipogenic transformation in OP9-DL1 cells and primary thymic stromal cells

  • Cell Biosci. 2019 Jun 14;9:48. doi: 10.1186/s13578-019-0311-1.
Jianxin Tan  1 ,  Yajun Wang  2 ,  Siliang Wang  3 ,  Simeng Wu  4 ,  Zhe Yuan  4 ,  Xike Zhu  2
Affiliations
  • 1. 1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004 People's Republic of China.
  • 2. 2Research Center, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004 People's Republic of China.
  • 3. 3Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, 110022 People's Republic of China.
  • 4. 4Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang, 110022 People's Republic of China.
PMID: 31249661 DOI: 10.1186/s13578-019-0311-1
Abstract

Background: Adipocyte accumulation is a predominant feature of age-related thymic involution, but the mechanisms responsible for thymic adipogenesis remain to be elucidated. The aim of this study was to identify key regulators in thymic adipogenesis. We used rosiglitazone, a potent Peroxisome Proliferator-activated Receptor γ (PPARγ) agonist, to induce adipogenic differentiation of OP9-DL1 cells, and investigated the differentially expressed proteins during adipogenic differentiation by using label-free quantitative proteomics. Furthermore, the effects of transforming growth factor β1 (TGF-β1) on rosiglitazone-induced adipogenic differentiation of OP9-DL1 cells as well as the underlying mechanisms were also investigated.

Results: Proteomic analysis identified 139 proteins differed significantly in rosiglitazone-treated cells compared with dimethyl sulphoxide (DMSO)-treated cells. Rosiglitazone-induced adipogenic differentiation was inhibited by TGF-β1 treatment in OP9-DL1 cells and primary thymic stromal cells. Real-Time PCR analysis showed significant increases in PPARγ and fatty acid binding protein 4 mRNA levels in rosiglitazone-treated cells, which were inhibited by TGF-β1 treatment. TGF-β1 down-regulated PPARγ expression at both mRNA and protein levels in OP9-DL1 cells. Chromatin immunoprecipitation analysis demonstrated that TGF-β1 enhanced the binding of SMAD2/3 and histone deacetylase 1, but reduced the binding of H3K14ac to the promoter of PPARγ gene. TGF-β1 partially reversed the inhibitory effects of rosiglitazone on the expression of Axin2 and β-catenin protein levels. TGF-β1 inhibited rosiglitazone-induced adipogenic transformation in OP9-DL1 cells by down-regulation of PPARγ and activation of the canonical Wnt/β-catenin signaling pathway.

Conclusion: Taken together, activation of TGF-β pathway may serve as a useful strategy to prevent thymic adiposity in age-related thymic involution.

Keywords
Adipocytes; PPARγ; Proteomics; TGF-β1; Thymic involution; Wnt/β-catenin.
Products