title: TGF-β Induces Up-Regulation of Chondroitin Sulfate Synthase 1 (CHSY1) in Nucleus Pulposus Cells Through MAPK Signaling.
abstract: OBJECTIVE
  Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-β can stimulate sulfated GAG production in nucleus pulposus cells; however, the underlying mechanisms are poorly understood.
  
  
  METHODS
  CHSY1 expression was examined in rat nucleus pulposus treated with TGF-β using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-β and to measure the effect of c-Jun and Sp1 on TGF-β mediated CHSY1 promoter activity and CHSY1 expression.
  
  
  RESULTS
  TGF-β increased CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway. Knockdown of c-Jun and Sp1 decreased CHSY1 promoter activity, CHSY1 expression and sGAG accumulation induced by TGF-β. Furthermore, we found that TGF-β-induced expression of CHSY1 was mediated through the activation of MAPK signaling. Moreover, we showed that silencing CHSY1 decreased sGAG accumulation in nucleus pulposus cells induced by TGF-β.
  
  
  CONCLUSIONS
  Our results suggest that TGF-β induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling.
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Changgui
authors.initials: C
authors.lastname: Shi
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.forename: Huajiang
authors.initials: H
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007403:Intervertebral Disc / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D064251:Multifunctional Enzymes / Q000378:metabolism*; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D064251:Multifunctional Enzymes; D016329:Sp1 Transcription Factor; D053782:Transforming Growth Factor beta3; C000608525:CHSY1 protein, rat; D017350:N-Acetylgalactosaminyltransferases; D014453:Glucuronosyltransferase