IL-13 did not lead to elevated Gremlin-1 expression nor did IL-11. In SSc cells siRNA mediated reduction of Gremlin-1 reduced collagen expression and CTGF gene and protein levels in these cells. Inhibition of Gremlin-1 overexpression cells with antibodies to TGF-β1 but not isotype controls led to reduced collagen and various TGF-β pathway chemical inhibitors also led to reduced collagen levels. This was associated with increased TGF-β1 levels and SBE luciferase activity but not increased Thrombospondin-1 expression. Overexpression also led to functional effects. Results: Overexpression of Gremlin-1 was achieved in primary dermal fibroblasts and lead to activation of quiescent cells to myofibroblasts indicated by collagen and α-Smooth muscle actin. Bleomycin was used as model of fibrosis and immunohistochemistry performed. Different cytokines were incubated with fibroblasts and Gremlin-1 measured. siRNA to Gremlin-1 in SSc dermal fibroblasts were performed to evaluate the role of Gremlin-1. Various inhibitors of TGF-β signaling and MAPK signaling were used post-transfection. Media Transfer experiments were performed to evaluate cytokine like effects.
Scratch wound assays were also performed. Various markers of myofibroblasts were measured at the mRNA and protein levels. Methods: Dermal fibroblasts were transfected with Grem1pcDNA3.1 expression vectors or empty vectors. Gremlin-1 is a BMP antagonist that is developmentally regulated and we sought to investigate its role in Systemic Sclerosis. The disease is characterized by activation of myofibroblasts but what governs this is unknown.
#SPACE GREMLIN PRO SKIN#
Objective: Systemic Sclerosis is an autoimmune connective tissue disease which results in fibrosis of the skin and lungs.
1Faculty of Health and Life Science, Northumbria University, Newcastle upon Tyne, United Kingdom.Distler 3, Richard Stratton 4 and Steven O’Reilly 2* Laura Duffy 1, John Henderson 1, Max Brown 2, Stefan Przyborski 2, Nicola Fullard 2, Lena Summa 3, Jorg H.
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