title: Decorin interacts with connective tissue growth factor (CTGF)/CCN2 by LRR12 inhibiting its biological activity.
abstract: Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation of the extracellular matrix occurs, mainly because of the action of the connective tissue growth factor (CTGF/CCN2). Little is known about how this growth factor activity is regulated. We found that decorin null myoblasts are more sensitive to CTGF than wild type myoblasts, as evaluated by the accumulation of fibronectin or collagen III. Decorin added exogenously negatively regulated CTGF pro-fibrotic activity and the induction of actin stress fibers. Using co-immunoprecipitation and in vitro interaction assays, decorin and CTGF were shown to interact in a saturable manner with a K(d) of 4.4 nM. This interaction requires the core protein of decorin. Experiments using the deletion mutant decorin indicated that the leucine-rich repeats (LRR) 10-12 are important for the interaction with CTGF and the negative regulation of the cytokine activity, moreover, a peptide derived from the LRR12 was able to inhibit CTGF-decorin complex formation and CTGF activity. Finally, we showed that CTGF specifically induced the synthesis of decorin, suggesting a mechanism of autoregulation. These results suggest that decorin interacts with CTGF and regulates its biological activity.
authors: Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, MIFAB, Pontificia Universidad Católica de Chile, Casilla 114-D, Santiago, Chile.
authors: Cecilia
authors: C
authors: Vial
authors: Jaime
authors: J
authors: Gutiérrez
authors: Cristian
authors: C
authors: Santander
authors: Daniel
authors: D
authors: Cabrera
authors: Enrique
authors: E
authors: Brandan
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D058575:Decorin / Q000235:genetics / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D051379:Mice; D008817:Mice, Mutant Strains; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology; D041681:NIH 3T3 Cells; D014176:Protein Biosynthesis / Q000235:genetics
chemical_list: C526318:CCN2 protein, mouse; C546879:Dcn protein, mouse; D058575:Decorin; D005353:Fibronectins; D046912:Multiprotein Complexes; D055513:Connective Tissue Growth Factor