Lumican is down-regulated in cells expressing endoglin. Evidence for an inverse correlationship between Endoglin and Lumican expression.
Endoglin (CD105) is a homodimeric membrane glycoprotein, which acts as a TGF-beta coreceptor in the vasculature and plays an important role in cardiovascular development and vascular remodelling. To isolate putative genes regulated by endoglin expression, a PCR-based RNA fingerprinting technique was carried out. Myoblasts stably transfected with endoglin showed a decrease in the expression of lumican both at the RNA and protein levels. Lumican is a proteoglycan of the extracellular matrix, belonging to the SLRP (Small Leucine-Rich Repeat Proteoglycans) family. Lumican down-regulation by endoglin appeared to be controlled, at least in part, at the transcriptional level, as indicated by RT-PCR, and transient transfection experiments using a lumican promoter reporter based vector. This inverse correlation between endoglin and lumican expression was substantiated by immunohistochemical staining of vessels from human tissues. Thus, cells belonging to the high endothelia, such as tonsil, express a large amount of endoglin, and the lumican content of their matrix is considerably reduced. Conversely, in resting endothelia, such as that of large vessels, the expression of endoglin is reduced whereas the amount of lumican is greatly increased. The inverse regulation in the expression of endoglin and lumican was also evident after TGF-beta treatments since endoglin was up-regulated, whereas lumican was down-regulated by this cytokine. This report describes for the first time a relationship between endoglin and lumican expression.
Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu, 9 Madrid, Spain.
Luisa M
LM
Botella
Francisco
F
Sanz-Rodriguez
Tilman
T
Sanchez-Elsner
Carmen
C
Langa
Jose R
JR
Ramirez
Calvin
C
Vary
Peter J
PJ
Roughley
Carmelo
C
Bernabeu
D000818:Animals; D015703:Antigens, CD; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D000071063:Endoglin; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007632:Keratan Sulfate / Q000235:genetics / Q000378:metabolism*; D000071234:Lumican; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D011508:Chondroitin Sulfate Proteoglycans; C064206:ENG protein, human; D000071063:Endoglin; C000604306:LUM protein, human; C000604308:Lum protein, rat; D000071234:Lumican; D011956:Receptors, Cell Surface; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D007632:Keratan Sulfate