Decorin deficiency leads to impaired angiogenesis in injured mouse cornea.
Small leucine-rich proteoglycans play important roles in the organization of the extracellular matrix as well as for the regulation of cell behavior; two biological processes that are essential for angiogenesis. We investigated consequences of the targeted ablation of decorin (DCN), biglycan (BGN) and fibromodulin (FMOD) genes on inflammation-induced angiogenesis in the cornea. In wild-type mice, DCN was localized exclusively to the corneal stroma, while FMOD and BGN were more prominently expressed in epithelial cells. Endothelial cells from limbus blood vessels expressed BGN and FMOD, but no DCN. However, after induction of angiogenesis by chemical cauterization, DCN was expressed in the newly formed capillaries, together with BGN and FMOD. Notably, in DCN-deficient mice, the growth of vessels was significantly diminished, whereas it did not significantly change in FMOD- or BGN-deficient animals. Moreover, blood vessels of DCN-deficient mice exhibited a similar expression level of BGN as control mice, while FMOD was increased on day 3 after injury. These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN.
Schönherr
Elke
E
Institute of Physiological Chemistry and Pathobiochemistry, University and University Hospital of Münster, Münster, Germany. schonherreh@cardiff.ac.uk
Sunderkötter
Cord
C
Schaefer
Liliana
L
Thanos
Solon
S
Grässel
Susanne
S
Oldberg
Ake
A
Iozzo
Renato V
RV
Young
Marian F
MF
Kresse
Hans
H
D000818:Animals; D058578:Biglycan; D003315:Cornea / Q000098:blood supply* / Q000502:physiology*; D003319:Corneal Stroma / Q000098:blood supply / Q000502:physiology; D058575:Decorin; D004728:Endothelium, Corneal / Q000098:blood supply / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics; D000071235:Fibromodulin; D007634:Keratitis / Q000503:physiopathology*; D016850:Limbus Corneae / Q000098:blood supply / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics*
C546885:Bgn protein, mouse; D058578:Biglycan; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604332:Fmod protein, mouse; D011509:Proteoglycans; D000071235:Fibromodulin