Follistatin Effects on the Activin Signalling Pathway in Human Nt2 and Fibroblasts from Dupuytrens Disease Tissue Essay

1691 WordsJun 3, 20137 Pages
Follistatin Effects on the Activin Signalling Pathway in human NT2 and Fibroblasts from Dupuytrens Disease Tissue Abstract Activins are cytokines belonging to the TGF-β superfamily and have numerous actions and target tissues within the body. Via the stimulation of FSH release from the pituitary, activin plays a significant role in the gonadal-pituitary axis. In addition to this reproductive function, activin and its Smad signalling pathway has been associated with increased collagen production leading to fibrotic tissue formation as seen in Dupuytrens disease. Known antagonists of activin signalling include follistatin, a secreted glycoprotein which bind to activin blocking its effects. To investigate activin signalling and the antagonistic effects of follistatin, we isolated and compared Smad activity and activin levels in Dupytrens disease fibroblasts and NT2 Sertoli like cell lines. ELISA assays demonstrated that Dupytrens fibroblasts contained far greater activin levels than NT2 cells. In cell lines treated with follistatin, Smad2 and Smad3 expression levels were found to be reduced in the disease tissue, thus suggesting a down regulation of the activin signalling pathway occurs in response to follistatin treatment. This highlights the potential therapeutic benefit of using treatments such as follistatin to disrupt activin signalling with the hope of reducing collagen production and disease pathology. Introduction Activin The transforming growth factor-β (TGF-β) superfamily members are often pleiotropic and multifunctional peptides implicated in a wide range of cell functions such as tissue homeostasis, immune responses, hormone secretion, as well as cell growth and differentiation (Schiller et al. 2004). Included in this family are the activins which act on the gonadal-pituitary axis positively regulating follicle stimulating

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