title: Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: Two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution.
abstract: Age-related thymic involution is characterized by a loss of thymic epithelial cells (TECs) and a concomitant increase in adipocytes, but the mechanisms involved in thymic adipogenesis are still not clear. Transforming growth factor β1 (TGF-β1) is a pleiotropic cytokine that has been reported to be up-regulated with age in thymic stromal cells in both human and mouse. However, the exact role of TGF-β1 in age-related thymic involution remains to be further elucidated. On the basis of previous findings, we propose a novel hypothesis that TGF-β1 functions a dual role in age-related thymic involution. On one hand, up-regulation of TGF-β1 promotes epithelial to mesenchymal transition (EMT) process in TECs via activating forkhead box protein C2 (FoxC2). On the other hand, TGF-β1 inhibits the transdifferentiation of EMT-derived mesenchymal cells to adipocytes in the thymus. If confirmed, our hypothesis will not only provide further evidence supporting that the transdifferentiation of TECs into pre-adipocytes represents a source of thymic adiposity during age-related thymic involution, but also uncover a unique role of TGF-β1 in the transdifferentiation of TECs into pre-adipocytes. Collectively, the inhibition of TGF-β1 may serve as a strategy to hinder age-related thymic involution or even to restore thymic function in the elderly.
authors.affiliation: Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Tan
authors.affiliation: Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.|Department of Nerve Function, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Xike
authors.initials: X
authors.lastname: Zhu
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000502:physiology*; D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D054338:Cell Transdifferentiation / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D051379:Mice; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1; C082078:mesenchyme fork head 1 protein
keywords: age-related thymic involution; epithelial to mesenchymal transition; thymic adipogenesis; transforming growth factor β1