Notch1 Inhibits Rosiglitazone-Induced Adipogenic Differentiation in Primary Thymic Stromal Cells

Frontiers in Pharmacology

Zhe Yuan¹  Simeng Wu¹  Hongmei Du²  Siliang Wang²  Xue Liu³  Yajun Wang³  Xike Zhu³  Jianxin Tan⁴ 

[1] Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang, China;Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, China;Research Center, Shengjing Hospital of China Medical University, Shenyang, China;State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China;

关键词: thymic adipogenesis;    thymic stromal cells;    RNA-seq;    Notch1;    autophagy;   

DOI  :  10.3389/fphar.2018.01284

来源: DOAJ

【 摘 要 】

Adipocyte deposition is believed to be a primary characteristic of age-related thymic involution. Herein, we cultured primary thymic stromal cells (TSCs), used rosiglitazone, a potent peroxisome proliferator-activated receptor γ (PPARγ) agonist, to induce adipogenic differentiation, and investigated the differentially expressed genes during adipogenic differentiation by using RNA-sequencing analysis. Furthermore, the effects of Notch1 on rosiglitazone-induced adipogenic differentiation of TSCs as well as the underlying mechanisms were also investigated. As a result, we identified a total of 1737 differentially expressed genes, among which 965 genes were up-regulated and 772 genes were down-regulated in rosiglitazone-treated cells compared with control cells. Gene ontology (GO) enrichment analysis showed that the GO terms were enriched in metabolic process, intracellular, and protein binding. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that a number of pathways, including ubiquitin mediated proteolysis, PPAR signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway were predominantly over-represented. Meanwhile, overexpression of Notch1 suppressed and inhibition of Notch1 promoted rosiglitazone-induced adipogenic differentiation in TSCs, and the pro-adipogenic effects of the Notch inhibitor DAPT were associated with the activation of autophagy. Taken together, our results suggest that Notch1 is a key regulator in thymic adipogenesis and may serve as a potential target to hinder thymic adiposity in age-related thymic involution.

【 授权许可】

Unknown