Transforming growth factor-beta 1 induces vascular endothelial growth factor expression in murine proximal tubular epithelial cells.

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Abstract

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-beta1 (TGF-beta1), lipopolysaccharides, interleukin-1beta, interleukin-10 and interferon-gamma, only TGF-beta1 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-beta1 detected by Northern blotting. Treatment with neutralizing anti-TGF-beta1 antibody abolished TGF-beta1-induced VEGF expression by 70%. Inhibitors of protein kinase C (PKC), Ro-31-8220 and staurosporin, significantly suppressed TGF-beta1-induced VEGF protein expression. These results demonstrate the role of TGF-beta1 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.

Original languageEnglish
JournalNephron - Experimental Nephrology
Volume95
Issue number2
Publication statusPublished - 2003

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Transforming Growth Factor beta
Vascular Endothelial Growth Factor A
Transforming Growth Factor beta1
Epithelial Cells
Kidney
Protein Kinase C
Cell Line
Proteins
Capillary Permeability
Interleukin-1beta
Mitogens
Angiotensin II
Northern Blotting
Interleukin-10
Reverse Transcription
Interferon-gamma
Lipopolysaccharides
Protein Isoforms
Endothelial Cells
Enzyme-Linked Immunosorbent Assay

Cite this

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title = "Transforming growth factor-beta 1 induces vascular endothelial growth factor expression in murine proximal tubular epithelial cells.",
abstract = "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-beta1 (TGF-beta1), lipopolysaccharides, interleukin-1beta, interleukin-10 and interferon-gamma, only TGF-beta1 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-beta1 detected by Northern blotting. Treatment with neutralizing anti-TGF-beta1 antibody abolished TGF-beta1-induced VEGF expression by 70{\%}. Inhibitors of protein kinase C (PKC), Ro-31-8220 and staurosporin, significantly suppressed TGF-beta1-induced VEGF protein expression. These results demonstrate the role of TGF-beta1 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.",
author = "Shinji Kitamura and Yohei Maeshima and Takeshi Sugaya and Hitoshi Sugiyama and Yasushi Yamasaki and Hirofumi Makino",
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T1 - Transforming growth factor-beta 1 induces vascular endothelial growth factor expression in murine proximal tubular epithelial cells.

AU - Kitamura, Shinji

AU - Maeshima, Yohei

AU - Sugaya, Takeshi

AU - Sugiyama, Hitoshi

AU - Yamasaki, Yasushi

AU - Makino, Hirofumi

PY - 2003

Y1 - 2003

N2 - 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-beta1 (TGF-beta1), lipopolysaccharides, interleukin-1beta, interleukin-10 and interferon-gamma, only TGF-beta1 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-beta1 detected by Northern blotting. Treatment with neutralizing anti-TGF-beta1 antibody abolished TGF-beta1-induced VEGF expression by 70%. Inhibitors of protein kinase C (PKC), Ro-31-8220 and staurosporin, significantly suppressed TGF-beta1-induced VEGF protein expression. These results demonstrate the role of TGF-beta1 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.

AB - 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-beta1 (TGF-beta1), lipopolysaccharides, interleukin-1beta, interleukin-10 and interferon-gamma, only TGF-beta1 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-beta1 detected by Northern blotting. Treatment with neutralizing anti-TGF-beta1 antibody abolished TGF-beta1-induced VEGF expression by 70%. Inhibitors of protein kinase C (PKC), Ro-31-8220 and staurosporin, significantly suppressed TGF-beta1-induced VEGF protein expression. These results demonstrate the role of TGF-beta1 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.

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