title: Effects of thymosin β4 and its N-terminal fragment Ac-SDKP on TGF-β-treated human lung fibroblasts and in the mouse model of bleomycin-induced lung fibrosis.
abstract: Thymosin β4 (Tβ4) and its amino-terminal fragment comprising N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) have been reported to act as anti-inflammatory and anti-fibrotic agents in vitro and in vivo. In recent papers, we have shown that Tβ4 exerts a widely protective role in mice treated with bleomycin, and in particular, we have demonstrated its inhibitory effects on both inflammation and early fibrosis.
  
  
  OBJECTIVE
  In this study, the putative anti-proliferative and anti-fibrogenic effects of Tβ4 and Ac-SDKP were evaluated in vitro. In addition, the effects of Tβ4 up to 21 days were evaluated in the bleomycin mouse model of lung fibrosis.
  
  
  METHODS
  We utilized both control and TGF-β-stimulated primary human lung fibroblasts isolated from both idiopathic pulmonary fibrosis (IPF) and control tissues. The in vivo effects of Tβ4 were assessed in CD1 mice treated with bleomycin.
  
  
  RESULTS
  In the in vitro experiments, we observed significant anti-proliferative effects of Ac-SDKP in IPF fibroblasts. In those cells, Ac-SDKP significantly inhibited TGF-β-induced α-SMA and collagen expression, hallmarks of fibroblast differentiation into myofibroblasts triggered by TGF-β. In vivo, despite its previously described protective role in mice treated with bleomycin at 7 days, Tβ4 failed to prevent fibrosis induced by the drug at 14 and 21 days.
  
  
  CONCLUSIONS
  We conclude that, compared to Tβ4, Ac-SDKP may have greater potential as an anti-fibrotic agent in the lung. Further in vivo experiments are warranted.
authors.affiliation: University of Catania, Department of Clinical and Experimental Medicine , Via Santa Sofia 78, 95123 Catania , Italy +39 095 378 1254 ; +39 095 378 1427 ; econte@unict.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Conte
authors.forename: Maria
authors.initials: M
authors.lastname: Iemmolo
authors.forename: Mary
authors.initials: M
authors.lastname: Fruciano
authors.forename: Evelina
authors.initials: E
authors.lastname: Fagone
authors.forename: Elisa
authors.initials: E
authors.lastname: Gili
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Carlo
authors.initials: C
authors.lastname: Vancheri
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D017434:Protein Structure, Tertiary; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D013947:Thymosin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D000099201:Thymosin beta(4)
chemical_list: D000893:Anti-Inflammatory Agents; D001761:Bleomycin; D009842:Oligopeptides; D013947:Thymosin; D016212:Transforming Growth Factor beta; D000099201:Thymosin beta(4); C058504:goralatide
keywords: Ac-SDKP; CD1 mice; COL-I; TGF-β1; bleomycin; human fibroblasts; idiopathic pulmonary fibrosis; lung fibrosis; thymosin β4; α-SMA