title: TGF-β stimulates biglycan core protein synthesis but not glycosaminoglycan chain elongation via Akt phosphorylation in vascular smooth muscle.
abstract: Transforming growth factor-β (TGF-β) can mediate proteoglycan synthesis via Smad and non-Smad signalling pathways in vascular smooth muscle (VSM). We investigated whether TGF-β-mediated proteoglycan synthesis is via PI3K/Akt. TGF-β induced a rapid phosphorylation of Akt that continued upto 4 h. Akt phosphorylation was blocked by Akt1/2 inhibitor SN30978; however, it did not block Smad2 phosphorylation at either the carboxy or linker regions indicating that TGF-β-mediated Akt phosphorylation is independent of Smad2 signalling. The role of Akt in TGF-β-mediated proteoglycan synthesis was investigated. Treatment with SN30978 showed a concentration-dependent decrease in TGF-β-mediated [(35)S]-sulphate and [(35)S]-Met/Cys incorporation into secreted proteoglycans; however, SDS-PAGE showed no change in biglycan size. In TGF-β-treated cells, biglycan mRNA levels increased by 40-100% in 24 h and was significantly blocked by SN30978. Our findings demonstrate that Akt is a downstream signalling component of TGF-β-mediated biglycan core protein synthesis but not glycosaminoglycan chain hyper-elongation in VSM.
authors.affiliation: Discipline of Pharmacy and Diabetes Complications Group, Health Innovations Research Institute, RMIT University, Bundoora, VIC, Australia. narin.osman@rmit.edu.au
authors.forename: Narin
authors.initials: N
authors.lastname: Osman
authors.forename: Robel
authors.initials: R
authors.lastname: Getachew
authors.forename: Micah
authors.initials: M
authors.lastname: Burch
authors.forename: Graeme
authors.initials: G
authors.lastname: Lancaster
authors.forename: Rikang
authors.initials: R
authors.lastname: Wang
authors.forename: Haitau
authors.initials: H
authors.lastname: Wang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
mesh_terms: D058578:Biglycan / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt