title: Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro.
abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-β (TGF-β). Conversely, migration toward ABA, but not toward TGF-β, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.
authors.affiliation: Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy. santina.bruzzone@unige.it
authors.forename: Santina
authors.initials: S
authors.lastname: Bruzzone
authors.forename: Florinda
authors.initials: F
authors.lastname: Battaglia
authors.forename: Elena
authors.initials: E
authors.lastname: Mannino
authors.forename: Alessia
authors.initials: A
authors.lastname: Parodi
authors.forename: Floriana
authors.initials: F
authors.lastname: Fruscione
authors.forename: Giovanna
authors.initials: G
authors.lastname: Basile
authors.forename: Annalisa
authors.initials: A
authors.lastname: Salis
authors.forename: Laura
authors.initials: L
authors.lastname: Sturla
authors.forename: Simone
authors.initials: S
authors.lastname: Negrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Kalli
authors.forename: Silvia
authors.initials: S
authors.lastname: Stringara
authors.forename: Gilberto
authors.initials: G
authors.lastname: Filaci
authors.forename: Elena
authors.initials: E
authors.lastname: Zocchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Fenoglio
mesh_terms: D000040:Abscisic Acid / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D010641:Phenotype; D010937:Plant Growth Regulators / Q000494:pharmacology*; D012595:Scleroderma, Systemic / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D010937:Plant Growth Regulators; D019715:Tissue Inhibitor of Metalloproteinase-1; D000040:Abscisic Acid; D020781:Matrix Metalloproteinase 1