Expression of endoglin in human mesangial cells: modulation of extracellular matrix synthesis

Abstract Transforming growth factor-β (TGF-β) has been identified as a key mediator of glomerulosclerosis in kidney diseases. Endoglin is a component of the TGF-β 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-β upregulated not only the expression of endoglin, but also that of TGF-β itself, TGF-β receptor type II, collagen I, collagen IV, and fibronectin. To study the role of endoglin in TGF-β responses, transfectant fibroblasts overexpressing endoglin were analyzed. Untreated and TGF-β-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.