Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

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• 作者：Santina Bruzzone^a ; ^b ; ^c ; ^{santina.bruzzone@unige.it} ; Florinda Battaglia^b ; Elena Mannino^a ; Alessia Parodi^b ; Floriana Fruscione^a ; ^c ; Giovanna Basile^a ; Annalisa Salis^a ; ^b ; Laura Sturla^a ; ^b ; Simone Negrini^b ; Francesca Kalli^b ; Silvia Stringara^b ; Gilberto Filaci^b ; ^d ; Elena Zocchi^a ; ^b ; ^c ; Daniela Fenoglio^b ; ^d
• 关键词：ABA ; abscisic acid ; TNF-¦Á ; tumor necrosis factor-¦Á ; LANCL2 ; lanthionine synthetase C-like protein 2 ; SSc ; systemic sclerosis ; FCS ; fetal calf serum ; TGF-¦Â ; transforming growth factor-¦Â ; CFDA-SE ; carboxyfluorescein succinimidyl ester ; FGF ; fibroblast g
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：25 May, 2012
• 年：2012
• 卷：422
• 期：1
• 页码：70-74
• 全文大小：479 K

文摘

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-¦Â (TGF-¦Â). Conversely, migration toward ABA, but not toward TGF-¦Â, 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.