Fibrotic response in fibroblasts from congenital disorders of glycosylation.
Bottom Line: The extent of this response was confirmed at the protein level by showing increased production of collagen type-I for example.This fibrotic response of CDG fibroblasts was not paralleled by a differentiation to myofibroblasts and by increased TGF-β signalling.We could show that the addition of recombinant IGFBP5, one of the induced proteins in CDG, to healthy control fibroblasts increased the production of collagen type-I to levels similar to those found in CDG fibroblasts.
Affiliation: Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.Show MeSH
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Mentions: The cytokine TGF-β is a prominent stimulus of ECM expression . To examine whether CDG fibroblasts are more sensitive to TGF-β than control fibroblasts, we treated CDG and control fibroblasts with the profibrotic cytokine TGF-β. The levels of collagen production were strongly increased in all treated cells with the exception of DPM1-CDG fibroblasts (Fig. 4). We also investigated whether CDG fibroblasts are more sensitive to TGF-β, considering the increased expression of endoglin in those cells. The levels of SMAD2 phosphorylation were measured in control and CDG fibroblasts stimulated with increasing amounts of TGF-β. This titration showed no clear difference of SMAD2 phosphorylation between control and CDG fibroblasts (Fig. 5). Finally, we investigated the activation of the TGF-β pathway by examining the level of SMAD4 nuclear localization in CDG and control fibroblasts. Also this parameter did not differ significantly between the cells examined (data not shown), indicating that the TGF-β pathway did not account for the increased ECM protein expression in CDG fibroblasts.
Affiliation: Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.