Decorin and biglycan of normal and pathologic human corneas.
OBJECTIVE
Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the core proteins that carry these atypical glycosaminoglycans. In this study the proteoglycan proteins attached to dermatan sulfate in normal and pathologic human corneas were examined to identify primary genes involved in the pathobiology of corneal scarring.


METHODS
Proteoglycans from human corneas with chronic edema, bullous keratopathy, and keratoconus and from normal corneas were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunoblotting, and immunohistology with peptide antibodies to decorin and biglycan.


RESULTS
Proteoglycans from pathologic corneas exhibit increased size heterogeneity and binding of the cationic dye alcian blue compared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribution patterns. In approximately half of the pathologic corneas, the level of biglycan was elevated an average of seven times above normal, and decorin was elevated approximately three times above normal. The increases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan sulfate chains of increased sulfation. Immunostaining of corneal sections showed an abnormal stromal localization of biglycan in pathologic corneas.


CONCLUSIONS
The increased dermatan sulfate associated with chronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compared with normal stromal proteoglycans.
Funderburgh
J L
JL
Division of Biology, Kansas State University, Manhattan 66506-4901, USA.
Hevelone
N D
ND
Roth
M R
MR
Funderburgh
M L
ML
Rodrigues
M R
MR
Nirankari
V S
VS
Conrad
G W
GW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058578:Biglycan; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000737:chemistry / Q000378:metabolism*; D003316:Corneal Diseases / Q000378:metabolism*; D058575:Decorin; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D011509:Proteoglycans / Q000302:isolation & purification / Q000378:metabolism*
C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans