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. (July 2015)

• Record Type: Journal Article
• Authors: Conte, Enrico; Iemmolo, Maria; Fruciano, Mary; Fagone, Evelina; Gili, Elisa; Genovese, Tiziana; Esposito, Emanuela; Cuzzocrea, Salvatore; Vancheri, Carlo
• Is Part Of: Expert opinion on biological therapy. Volume 15:Number 1(2015:Jan.)
• Page Start: 211
• Page End: 221
• Publication Date: 2015-07
• Subjects: Gene therapy -- Periodicals; Protein drugs -- Periodicals; Peptide drugs -- Periodicals; Immunotherapy -- Periodicals; Drug delivery systems -- Periodicals; 615.5
• DOI: 10.1517/14712598.2015.1026804
• Languages: English
• ISSNs: 1471-2598

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>in vitro</italic> and <italic>in vivo.</italic> 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.</p> <p> <bold> <italic>Objectives:</italic> </bold> In this study, the putative anti-proliferative and anti-fibrogenic effects of Tβ4 and Ac-SDKP were evaluated <italic>in vitro.</italic> In addition, the effects of Tβ4 up to 21 days were evaluated in the bleomycin mouse model of lung fibrosis.</p> <p> <bold> <italic>Methods:</italic> </bold> We utilized both control and TGF-β-stimulated primary human lung fibroblasts isolated from both idiopathic pulmonary fibrosis (IPF) and control tissues. The <italic>in vivo</italic> effects of Tβ4 were assessed in CD1 mice treated with bleomycin.</p> <p> <bold> <italic>Results:</italic> </bold> In the <italic>in vitro</italic> 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. <italic>In vivo, </italic> 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.</p> <p> <bold> <italic>Conclusion:</italic> </bold> We conclude that, compared to Tβ4, Ac-SDKP may have greater potential as an anti-fibrotic agent in the lung. Further <italic>in vivo</italic> experiments are warranted.</p> </abstract>