Expression of endoglin in human mesangial cells: modulation of extracellular matrix synthesis.
Transforming growth factor-beta (TGF-beta) has been identified as a key mediator of glomerulosclerosis in kidney diseases. Endoglin is a component of the TGF-beta receptor system that is upregulated during glomerulosclerosis, suggesting a role during progression of renal diseases characterized by extracellular matrix (ECM) synthesis and accumulation. The expression of endoglin was demonstrated in cultured human mesangial cells (HMC) by flow cytometry, Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot analyses. TGF-beta upregulated not only the expression of endoglin, but also that of TGF-beta itself, TGF-beta receptor type II, collagen I, collagen IV, and fibronectin. To study the role of endoglin in TGF-beta responses, transfectant fibroblasts overexpressing endoglin were analyzed. Untreated and TGF-beta-treated endoglin(+) cells showed significantly lower levels of collagens than those in control cells, indicating that endoglin negatively regulates ECM levels of collagens. These findings may have important implications in the pathological states associated with renal fibrosis.
Diez-Marques
Luisa
L
Department of Physiology, Faculty of Medicine, Alcala University, Alcala de Henares, Madrid, Spain.
Ortega-Velazquez
Rocio
R
Langa
Carmen
C
Rodriguez-Barbero
Alicia
A
Lopez-Novoa
Jose Miguel
JM
Lamas
Santiago
S
Bernabeu
Carmelo
C
D015703:Antigens, CD; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D000071063:Endoglin; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D003094:Collagen