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: To validate the up-regulation of ECM components at the protein level, we first measured collagen production in fibroblasts. Using the Sircol dye assay, we detected elevated collagen concentrations in all CDG fibroblasts tested (Fig. 2A). The increased collagen production was confirmed by immunofluorescence analysis of fibroblasts performed with an antibody to collagen type-I (Fig. 2B). The induction of ECM components in CDG was also confirmed by Western blot analysis of the proteins IGFBP5, COMP, endoglin and PSG1 (Fig. 3), whereas the production of ECM proteins by fibroblasts is often associated to myofibroblastic differentiation, such a phenotype was not observed in CDG fibroblasts, as assessed by the low level of the myofibroblast marker protein α-smooth muscle actin  (data not shown).
Affiliation: Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.