Production and Biochemical Characterization of Dimeric Recombinant Gremlin-1
Stefania Mitola,Cosetta Ravelli,Michela Corsini,Alessandra Gianoncelli,Federico Galvagni,Kurt Ballmer-Hofer,Marco Presta,Elisabetta Grillo +7 more
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TLDR
A multi-step approach for the expression and purification of homodimeric, fully active, histidine-tagged recombinant gremlin-1, using mammalian HEK293T cells enables obtaining a highly pure recombinant dimeric g Kremlin-1 protein, exhibiting both BMP antagonist and potent VEGFR2 agonist activities.Abstract:
Gremlin-1 is a secreted cystine-knot protein that acts as an antagonist of bone morphogenetic proteins (BMPs), and as a ligand of heparin and the vascular endothelial growth factor receptor 2 (VEGFR2), thus regulating several physiological and pathological processes, including embryonic development, tissue fibrosis and cancer. Gremlin-1 exerts all these biological activities only in its homodimeric form. Here, we propose a multi-step approach for the expression and purification of homodimeric, fully active, histidine-tagged recombinant gremlin-1, using mammalian HEK293T cells. Ion metal affinity chromatography (IMAC) of crude supernatant followed by heparin-affinity chromatography enables obtaining a highly pure recombinant dimeric gremlin-1 protein, exhibiting both BMP antagonist and potent VEGFR2 agonist activities.read more
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The impact of adipokines on vascular networks in adipose tissue
Vliora Maria,Ravelli Cosetta,Grillo Elisabetta,Corsini Michela,D. Flouris Andreas,Mitola Stefania +5 more
TL;DR: In this paper , the role of adipokines in the regulation of angiogenesis was investigated and a better understanding of the link between adipokine and angiogenic will open the way for novel therapeutic approaches to treat obesity and metabolic diseases.
Journal ArticleDOI
Role of gremlin-1 in the pathophysiology of the adipose tissues.
Elisabetta Grillo,Cosetta Ravelli,Georgia Colleluori,Francesco D’Agostino,Mattia Domenichini,Antonio Giordano,Stefania Mitola +6 more
TL;DR: Gremlin-1 is a secreted bone morphogenetic protein (BMP) antagonist playing a pivotal role in the regulation of tissue formation and embryonic development as mentioned in this paper , which has been shown to be a multifunctional factor involved in wound healing, inflammation, cancer and tissue fibrosis.
Journal ArticleDOI
The impact of adipokines on vascular networks in adipose tissue.
Maria Vliora,Cosetta Ravelli,Elisabetta Grillo,Michela Corsini,Andreas D. Flouris,Stefania Mitola +5 more
TL;DR: In this paper , the role of adipokines in the regulation of angiogenesis was investigated and a better understanding of the link between adipokine and angiogenic will open the way for novel therapeutic approaches to treat obesity and metabolic diseases.
Journal ArticleDOI
Mechanobiology of the relocation of proteins in advecting cells: in vitro experiments, multi-physics modeling, and simulations.
Mattia Serpelloni,Matteo Arricca,Cosetta Ravelli,Elisabetta Grillo,Stefania Mitola,A. Salvadori +5 more
TL;DR: In this paper , a fully coupled multi-physics model was developed to capture and predict the protein flow on endothelial advecting plasma membranes, and the model has been validated against co-designed in vitro experiments.
References
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Journal ArticleDOI
Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis.
TL;DR: G Rem1-mediated BMP antagonism is essential to induce metanephric kidney development as initiation of ureter growth, branching and establishment of RET/GDNF feedback signaling are disrupted in Grem1-deficient embryos.
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Comparative genomic analysis of the eight-membered ring cystine knot-containing bone morphogenetic protein antagonists.
TL;DR: Based on the known three-dimensional structure of key cystine knot proteins, it is postulated disulfide bondings for eight-membered ring BMP antagonists to predict their potential folding and dimerization.
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Effect of Increased Expression of Protein Disulfide Isomerase and Heavy Chain Binding Protein on Antibody Secretion in a Recombinant CHO Cell Line
TL;DR: Recombinant CHO cells were transfected with PDI or BIP alone or in combination, and the effect on intracellular light and heavy chain content and specific production rate was determined.
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Gremlin is a novel agonist of the major proangiogenic receptor VEGFR2
Stefania Mitola,Cosetta Ravelli,Emanuela Moroni,Valentina Salvi,Daria Leali,Kurt Ballmer-Hofer,Luca Zammataro,Marco Presta +7 more
TL;DR: Gremlin represents a novel proangiogenic VEGFR2 agonist distinct from the VEGF family ligands with implications in vascular development, angiogenesis-dependent diseases, and tumor neovascularization.
Journal ArticleDOI
Bone morphogenetic protein-4 inhibitor gremlin is overexpressed in idiopathic pulmonary fibrosis.
Katri Koli,Marjukka Myllärniemi,Kirsi Vuorinen,Kaisa Salmenkivi,Merja Johanna Ryynänen,Vuokko L. Kinnula,Jorma Keski-Oja +6 more
TL;DR: The overexpression of this developmental gene in IPF may be a key event in the persistence of myofibroblasts in the lung interstitium and provides a potential target for therapeutic intervention.