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 observed increased expression of IGFBP5 in CDG was unexpected. The IGFBP5 protein has been associated to pulmonary fibrosis, where IGFBP5 has been shown to stimulate the production of ECM proteins by activating fibroblasts . Therefore, we did test whether the increased IGFBP5 expression in CDG fibroblasts could be related to the increased production of ECM components in these cells. We incubated control fibroblasts with recombinant IGFBP5 at increasing concentrations. The addition of IGFBP5 at 0.25 μg/ml was sufficient to increase the level of collagen production after 2 days, whereas this effect was highest at an IGFBP5 concentration of 1.5 μg/ml (Fig. 6). This effect was similar to that obtained when stimulating fibroblasts with 10 ng/ml of TGF-β.
Affiliation: Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.