Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly
Open Access
- 8 December 2020
- Vol. 9 (12), 2646
- https://doi.org/10.3390/cells9122646
Abstract
Proper processing of collagens COL1 and COL6 is required for normal function of adipose tissue and skeletal muscle. Proteoglycan decorin (DCN) regulates collagen fiber formation. The amino-terminus of DCN is modified with an O-linked glycosaminoglycan (GAG), the function of which has remained unclear. Previously, non-glycanated DCN (ngDCN) was identified as a marker of adipose stromal cells. Here, we identify MMP14 as the metalloprotease that cleaves DCN to generate ngDCN. We demonstrate that mice ubiquitously lacking DCN GAG (ngDCN mice) have reduced matrix rigidity, enlarged adipocytes, fragile skin, as well as skeletal muscle hypotrophy, fibrosis, and dysfunction. Our results indicate that DCN deglycanation results in reduced intracellular DCN—collagen binding and increased production of truncated COL6 chains, leading to aberrant procollagen processing and extracellular localization. This study reveals that the GAG of DCN functions to regulate collagen assembly in adipose tissue and skeletal muscle and uncovers a new mechanism of matrix dysfunction in obesity and aging.This publication has 79 references indexed in Scilit:
- Age-dependent alterations of decorin glycosaminoglycans in human skinScientific Reports, 2013
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- In Vivo Identification of Bipotential Adipocyte Progenitors Recruited by β3-Adrenoceptor Activation and High-Fat FeedingCell Metabolism, 2012
- Dichotomous effects of VEGF-A on adipose tissue dysfunctionProceedings of the National Academy of Sciences of the United States of America, 2012
- The extracellular matrix: A dynamic niche in cancer progressionThe Journal of cell biology, 2012
- Characterization of Pdgfrb‐Cre transgenic mice reveals reduction of ROSA26 reporter activity in remodeling arteriesgenesis, 2011
- Secreted Versus Membrane-anchored Collagenases: RELATIVE ROLES IN FIBROBLAST-DEPENDENT COLLAGENOLYSIS AND INVASIONOnline Journal of Public Health Informatics, 2009
- Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VIMolecular and Cellular Biology, 2009
- Mesenchymal Stem Cells: Revisiting History, Concepts, and AssaysCell Stem Cell, 2008
- Matrix metalloproteinases and the regulation of tissue remodellingNature Reviews Molecular Cell Biology, 2007