Transforming Growth Factor-β1 Induces Vascular Endothelial Growth Factor Expression in Murine Proximal Tubular Epithelial CellsKitamura S.a · Maeshima Y.a · Sugaya T.b · Sugiyama H.a · Yamasaki Y.a · Makino H.a
aDepartment of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, and bCenter for Tsukuba Advanced Research Alliance, University of Tsukuba Research Laboratory, Tsukuba, Japan
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Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that promotes angiogenesis, vasculogenesis, and increases vascular permeability. VEGF is expressed in renal tubular epithelial cells and urinary VEGF excretion is increased in various glomerular disorders. However, the mechanisms underlying expression of VEGF in renal tubular epithelial cells have not been fully elucidated. In the present study, we attempted to define a predominant regulator of VEGF expression using a cultured murine renal proximal tubular epithelial cell line (mProx24). VEGF protein concentration in the culture supernatant was measured by sandwich enzyme-linked immunosorbent assay. mProx24 constitutively produced VEGF at low level. Major isoforms expressed in this cell line were VEGF164 and VEGF120 determined by reverse transcription-polymerase chain reaction method. Among various stimuli including angiotensin II, transforming growth factor-β1 (TGF-β1), lipopolysaccharides, interleukin-1β, interleukin-10 and interferon-γ, only TGF-β1 significantly increased the level of VEGF protein at 24 h in a dose-dependent manner. The steady-state mRNA level of VEGF was dose dependently increased by TGF-β1 detected by Northern blotting. Treatment with neutralizing anti-TGF-β1 antibody abolished TGF-β1-induced VEGF expression by 70%. Inhibitors of protein kinase C (PKC), Ro-31-8220 and staurosporin, significantly suppressed TGF-β1-induced VEGF protein expression. These results demonstrate the role of TGF-β1 on the expression of VEGF in proximal tubular epithelial cells mediated potentially via PKC pathway. This regulatory mechanism may be associated with the progression of tubulointerstitial lesions in renal disorders.
© 2003 S. Karger AG, Basel
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