title: Role of serotonergic system in the pathogenesis of fibrosis in canine idiopathic inflammatory myopathies.
abstract: Idiopathic inflammatory myopathies are muscle diseases characterized by inflammation, necrosis, and fibrosis. The neurotransmitter serotonin (5-HT) has been shown to promote fibrosis in many tissues and organs by activating TGFβ-1 signaling. In this study, we evaluated the potential role of 5-HT in the pathogenesis of fibrosis in canine idiopathic inflammatory myopathies. Muscle biopsies from dogs affected by masticatory muscle myositis or polymyositis and from healthy dogs were processed for immunohistochemistry and Western blotting. The immunohistochemical analysis showed a strong expression of 5-HT in muscle tissues of affected dogs, whereas the amine was absent in the muscles of healthy dogs. Biochemical analysis showed increased expression levels of the selective 5-HT2A receptor in the muscle specimens of the most severely affected dogs versus controls. Further, increased phosphorylation levels of the TGFβ-1 signaling mediators SMAD2/3 and ERK1/2 were detected in tissue samples from affected dogs as compared to tissues from healthy dogs. Although further studies are needed, our findings highlight for the first time a potential role of 5-HT in the development of fibrosis in canine idiopathic inflammatory myopathies, thus supporting other evidence that 5-HT pro-fibrotic activity occurs via activation of TGFβ-1 signaling pathway.
authors.affiliation: Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
authors.forename: Luigi Michele
authors.initials: LM
authors.lastname: Pavone
authors.forename: Silvana
authors.initials: S
authors.lastname: Rea
authors.forename: Francesca
authors.initials: F
authors.lastname: Trapani
authors.forename: Valeria
authors.initials: V
authors.lastname: De Pasquale
authors.forename: Simona
authors.initials: S
authors.lastname: Tafuri
authors.forename: Serenella
authors.initials: S
authors.lastname: Papparella
authors.forename: Orlando
authors.initials: O
authors.lastname: Paciello
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009220:Myositis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D010766:Phosphorylation; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin