ArticlePloS one2012
Ets-1 is essential for connective tissue growth factor (CTGF/CCN2) induction by TGF-β1 in osteoblasts.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Xanthohumol overcomes osimertinib resistance via governing ubiquitination-modulated Ets-1 turnover.Cell death discovery · 2024Article
- Effect of strontium on transcription factors identified by transcriptome analyses of bovine ruminal epithelial cells.BMC veterinary research · 2024Article
- Signaling Pathway of Taurine-Induced Upregulation of TXNIP.Metabolites · 2022Article
- TGF‑β1 affects the renal cancer miRNome and regulates tumor cells proliferation.International journal of molecular medicine · 2022Article
- Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.Acta pharmaceutica Sinica. B · 2022Review
- HPV16-transformed human keratinocytes depend on SIX1 expression for proliferation and HPV E6/E7 gene expression.Virology · 2019Article
- Unique mechanisms of connective tissue growth factor regulation in airway smooth muscle in asthma: Relationship with airway remodelling.Journal of cellular and molecular medicine · 2018Article
- Multiple enhancer regions govern the transcription of CCN2 during embryonic development.Journal of cell communication and signaling · 2018Article
- Inhibiting cell migration and cell invasion by silencing the transcription factor ETS-1 in human bladder cancer.Oncotarget · 2016Article
- ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling.Scientific reports · 2015Article
- Activation of PPAR-γ inhibits differentiation of rat osteoblasts by reducing expression of connective tissue growth factor.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014Article
- TGFβ receptor I transactivation mediates stretch-induced Pak1 activation and CTGF upregulation in mesangial cells.Journal of cell science · 2013Article
- Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.Matrix biology : journal of the International Society for Matrix Biology · 2013Review
- Genome-wide and candidate gene association studies of placental abruption.International journal of molecular epidemiology and genetics · 2013Article
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6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEts-1 controls osteoblast differentiation and bone development; however, its downstream mechanism of action in osteoblasts remains largely undetermined. CCN2 acts as an anabolic growth factor to regulate osteoblast differentiation and function. CCN2 is induced by TGF-β1 and acts as a mediator of TGF-β1 induced matrix production in osteoblasts; however, the molecular mechanisms that control CCN2 induction are poorly understood. In this study, we investigated the role of Ets-1 for CCN2 induction by TGF-β1 in primary osteoblasts.
resultsWe demonstrated that Ets-1 is expressed and induced by TGF-β1 treatment in osteoblasts, and that Ets-1 over-expression induces CCN2 protein expression and promoter activity at a level similar to TGF-β1 treatment alone. Additionally, we found that simultaneous Ets-1 over-expression and TGF-β1 treatment synergize to enhance CCN2 induction, and that CCN2 induction by TGF-β1 treatment was impaired using Ets-1 siRNA, demonstrating the requirement of Ets-1 for CCN2 induction by TGF-β1. Site-directed mutagenesis of eight putative Ets-1 motifs (EBE) in the CCN2 promoter demonstrated that specific EBE sites are required for CCN2 induction, and that mutation of EBE sites in closer proximity to TRE or SBE (two sites previously shown to regulate CCN2 induction by TGF-β1) had a greater effect on CCN2 induction, suggesting potential synergetic interaction among these sites for CCN2 induction. In addition, mutation of EBE sites prevented protein complex binding, and this protein complex formation was also inhibited by addition of Ets-1 antibody or Smad 3 antibody, demonstrating that protein binding to EBE motifs as a result of TGF-β1 treatment require synergy between Ets-1 and Smad 3.
conclusionsThis study demonstrates that Ets-1 is an essential downstream signaling component for CCN2 induction by TGF-β1 in osteoblasts, and that specific EBE sites in the CCN2 promoter are required for CCN2 promoter transactivation in osteoblasts.
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