title: Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?
abstract: Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD).
authors.affiliation: Department of Sensory Organs, "Sapienza" University of Rome, Rome.
authors.forename: Enrica
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Department of Sensory Organs, "Sapienza" University of Rome, Rome.
authors.forename: Samanta
authors.initials: S
authors.lastname: Taurone
authors.affiliation: Department of Neurology and Psychiatry, "Sapienza" University of Rome, Rome.
authors.forename: Lia
authors.initials: L
authors.lastname: Bardella
authors.affiliation: Department of Oncological Sciences, S. Andrea Hospital, "Sapienza" University of Rome, Rome.
authors.forename: Alberto
authors.initials: A
authors.lastname: Signore
authors.affiliation: Department of Anatomical, Histological, Forensic and Locomotor System Sciences, "Sapienza" Univ. of Rome, Rome.
authors.forename: Elena
authors.initials: E
authors.lastname: Pompili
authors.affiliation: Division of Orthopedics, S. Giovanni Calibita Fatebenefratelli Hospital, Rome.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Sessa
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Latina.
authors.forename: Caterina
authors.initials: C
authors.lastname: Chiappetta
authors.affiliation: Department of Anatomical, Histological, Forensic and Locomotor System Sciences, "Sapienza" Univ. of Rome, Rome.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fumagalli
authors.affiliation: Department of Radiology, Oncology and Pathology, "Sapienza" University of Rome, Rome.
authors.forename: Cira
authors.initials: C
authors.lastname: Di Gioia
authors.affiliation: Department of Systems Medicine, "Tor Vergata" University of Rome, Rome.
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Pastore
authors.affiliation: Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Scarpa
authors.affiliation: Department of Sensory Organs, "Sapienza" University of Rome, Rome marco.artico@uniroma1.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Artico
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D004387:Dupuytren Contracture / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A
keywords: Dupuytren's contracture; cytokines; growth factors; immunohistochemistry (IHC); myofibroblasts