TY - JOUR
T1 - Distinct effects of different matrix proteoglycans on collagen fibrillogenesis and cell-mediated collagen reorganization
AU - Chen, Dongning
AU - Smith, Lucas R.
AU - Khandekar, Gauri
AU - Patel, Pavan
AU - Yu, Christopher K.
AU - Zhang, Kehan
AU - Chen, Christopher S.
AU - Han, Lin
AU - Wells, Rebecca G.
N1 - Funding Information:
This work was supported by the UPenn National Science Foundation MRSEC (DMR-1720530), by the Center for Engineering MechanoBiology (CEMB), a National Science Foundation Science and Technology Center (under grant agreement CMMI:15-48571), and by grant R01 EB017753 (to RGW). We are grateful to Gordon Ruthel and the Penn Vet imaging Core for extensive assistance with SHG imaging; Yuri Veklich and the University of Pennsylvania Cell and Developmental Biology Microscopy Core for help with SEM; and the Image Analysis and Gene Expression Quantification Core of the National Institute of Diabetes, Digestive and Kidney Diseases Center for Molecular Studies in Digestive and Liver Diseases (NIH P30 DK050306). The versican antibody 12C5 developed by R.A. Asher was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen behaviors. The different ways in which matrix PGs interact with collagen have important implications for understanding the role of the ECM in diseases such as fibrosis and cancer, and suggest that matrix PGs are potential therapeutic targets.
AB - The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen behaviors. The different ways in which matrix PGs interact with collagen have important implications for understanding the role of the ECM in diseases such as fibrosis and cancer, and suggest that matrix PGs are potential therapeutic targets.
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U2 - 10.1038/s41598-020-76107-0
DO - 10.1038/s41598-020-76107-0
M3 - Article
C2 - 33149218
AN - SCOPUS:85094952334
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 19065
ER -