Genetic evidence for the coordinated regulation of collagen fibrillogenesis in the cornea by decorin and biglycan.
Publication/Presentation Date
3-27-2009
Abstract
Decorin and biglycan are class I small leucine-rich proteoglycans (SLRPs) involved in regulation of collagen fibril and matrix assembly. We hypothesize that tissue-specific matrix assembly, such as in the cornea, requires a coordinate regulation involving multiple SLRPs. To this end, we investigated the expression of decorin and biglycan in the cornea of mice deficient in either SLRP gene and in double-mutant mice. Decorin and biglycan exhibited overlapping spatial expression patterns throughout the corneal stroma with differential temporal expression. Whereas decorin was expressed at relatively high levels in all developmental stages, biglycan expression was high early, decreased during development, and was present at very low levels in the mature cornea. Ultrastructural analyses demonstrated comparable fibril structure in the decorin- and biglycan-null corneas compared with wild-type controls. We found a compensatory up-regulation of biglycan gene expression in the decorin-deficient mice, but not the reverse. Notably, the corneas of compound decorin/biglycan-null mice showed severe disruption in fibril structure and organization, especially affecting the posterior corneal regions, corroborating the idea that biglycan compensates for the loss of decorin. Fibrillogenesis assays using recombinant decorin and biglycan confirmed a functional compensation, with both having similar effects at high SLRP/collagen ratios. However, at low ratios decorin was a more efficient regulator. The use of proteoglycan or protein core yielded comparable results. These findings provide firm genetic evidence for an interaction of decorin and biglycan during corneal development and further suggest that decorin has a primary role in regulating fibril assembly, a function that can be fine-tuned by biglycan during early development.
Volume
284
Issue
13
First Page
8888
Last Page
8897
ISSN
0021-9258
Published In/Presented At
Zhang, G., Chen, S., Goldoni, S., Calder, B. W., Simpson, H. C., Owens, R. T., McQuillan, D. J., Young, M. F., Iozzo, R. V., & Birk, D. E. (2009). Genetic evidence for the coordinated regulation of collagen fibrillogenesis in the cornea by decorin and biglycan. The Journal of biological chemistry, 284(13), 8888–8897. https://doi.org/10.1074/jbc.M806590200
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
19136671
Department(s)
Administration and Leadership
Document Type
Article