title: Preventive and therapeutic effects of thymosin β4 N-terminal fragment Ac-SDKP in the bleomycin model of pulmonary fibrosis.
abstract: In this study, the bleomycin model of pulmonary fibrosis was utilized to investigate putative anti-fibrotic activity of Ac-SDKP in vivo. Male CD-1 mice received intra-tracheal bleomycin (BLEO, 1 mg/kg) instillation in the absence or presence of Ac-SDKP (a dose of 0.6 mg/kg delivered intra-peritoneally on the day of BLEO treatment, d0, followed by bi-weekly additional doses). To evaluate therapeutic effects in a subset of mice, Ac-SDKP was administered one week after BLEO instillation (d7). Animals were sacrificed at one, two, or three weeks later. Measurement of fluid and collagen content in the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, lung histology, immunohistochemistry (IHC), and molecular analysis were performed. Compared to BLEO-treated mice, animals that received also Ac-SDKP (at both d0 and d7) had significantly decreased mortality, weight loss, inflammation (edema, and leukocyte lung infiltration), lung damage (histological evidence of lung injury), and fibrosis (collagen histological staining and soluble collagen content in the lung) at up to 21 days. Moreover, IHC and quantitative RT-PCR results demonstrated a significant decrease in BLEO-induced IL-17 and TGF-β expression in lung tissue. Importantly, α-SMA expression, the hallmark of myofibroblast differentiation, was also decreased. This is the first report showing not only a preventive protective role of Ac-SDKP but also its significant therapeutic effects in the bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Conte
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Evelina
authors.initials: E
authors.lastname: Fagone
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gili
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Mary
authors.initials: M
authors.lastname: Fruciano
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Iemmolo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Maria Provvidenza
authors.initials: MP
authors.lastname: Pistorio
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98166 Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98166 Messina, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Cordaro
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98166 Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vancheri
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001761:Bleomycin; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000199:Actins; D020381:Interleukin-17; D009842:Oligopeptides; D020011:Protective Agents; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D001761:Bleomycin; D003094:Collagen; C058504:goralatide
keywords: Ac-SDKP; IPF; bleomycin; lung fibrosis; mouse