7 Citations (Scopus)

Abstract

Urotensin-II (UII) is a potent vasoactive peptide that has been implicated in cardiac fibrosis and renal diseases. However, the role played by UII in renal tissues is largely unknown. In this study, we investigated the effects of human UII (hUII) on rat renal proximal tubular cells of the NRK-52E line and the role of Src homology 2-containing phosphotyrosine phosphatase (SHP-2) in the hUII-induced transactivation of the epidermal growth factor receptor (EGFR). Exposure to hUII at low concentrations significantly induced proliferation in NRK-52E cells; this effect was inhibited by treatment with an ERK1/2 inhibitor (PD98059). UII treatment increased the phosphorylation of EGFR and induced the generation of reactive oxygen species (ROS). Treatment of the ROS scavenger N-acetyl-cysteine (NAC) inhibited EGFR transactivation and ERK phosphorylation induced by hUII. SHP-2 was found to interact with EGFR and be transiently oxidized following the hUII treatment. In SHP-2 knockdown cells, UII-induced phosphorylation of EGFR was less influenced by NAC, and significantly suppressed by heparin binding (HB)-EGF neutralizing antibody. Our data suggest that the ROS-mediated oxidation of SHP-2 is essential for the hUII-induced mitogenic pathway in NRK-52E cells.

Original languageEnglish
Pages (from-to)155-162
Number of pages8
JournalGrowth Factors
Volume27
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Epidermal Growth Factor Receptor
Transcriptional Activation
Rats
Cells
Phosphorylation
Kidney
Cell Line
Oxidation
Acetylcysteine
Reactive Oxygen Species
Cysteine
Protein Tyrosine Phosphatases
Neutralizing Antibodies
Epidermal Growth Factor
Heparin
urotensin II
Tissue
Fibrosis
Peptides

Keywords

  • Epidermal growth factor receptor transactivation
  • Rat renal proximal tubular cells
  • Reactive oxygen species
  • Src homology 2-containing phosphotyrosine phosphatase
  • Urotensin II

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology
  • Medicine(all)

Cite this

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title = "Urotensin II induces transactivation of the epidermal growth factor receptor via transient oxidation of SHP-2 in the rat renal tubular cell line NRK-52E",
abstract = "Urotensin-II (UII) is a potent vasoactive peptide that has been implicated in cardiac fibrosis and renal diseases. However, the role played by UII in renal tissues is largely unknown. In this study, we investigated the effects of human UII (hUII) on rat renal proximal tubular cells of the NRK-52E line and the role of Src homology 2-containing phosphotyrosine phosphatase (SHP-2) in the hUII-induced transactivation of the epidermal growth factor receptor (EGFR). Exposure to hUII at low concentrations significantly induced proliferation in NRK-52E cells; this effect was inhibited by treatment with an ERK1/2 inhibitor (PD98059). UII treatment increased the phosphorylation of EGFR and induced the generation of reactive oxygen species (ROS). Treatment of the ROS scavenger N-acetyl-cysteine (NAC) inhibited EGFR transactivation and ERK phosphorylation induced by hUII. SHP-2 was found to interact with EGFR and be transiently oxidized following the hUII treatment. In SHP-2 knockdown cells, UII-induced phosphorylation of EGFR was less influenced by NAC, and significantly suppressed by heparin binding (HB)-EGF neutralizing antibody. Our data suggest that the ROS-mediated oxidation of SHP-2 is essential for the hUII-induced mitogenic pathway in NRK-52E cells.",
keywords = "Epidermal growth factor receptor transactivation, Rat renal proximal tubular cells, Reactive oxygen species, Src homology 2-containing phosphotyrosine phosphatase, Urotensin II",
author = "Sue, {Yuh Mou} and Chen, {Cheng Hsien} and Hsu, {Yung Ho} and Chun-Cheng Hou and Cheng, {Chung Yi} and Chen, {Yen Cheng} and Lin, {Shih Li} and Tzen-Wen Chen and Chen, {Tso Hsiao}",
year = "2009",
doi = "10.1080/08977190902879866",
language = "English",
volume = "27",
pages = "155--162",
journal = "Growth Factors",
issn = "0897-7194",
publisher = "Informa Healthcare",
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T1 - Urotensin II induces transactivation of the epidermal growth factor receptor via transient oxidation of SHP-2 in the rat renal tubular cell line NRK-52E

AU - Sue, Yuh Mou

AU - Chen, Cheng Hsien

AU - Hsu, Yung Ho

AU - Hou, Chun-Cheng

AU - Cheng, Chung Yi

AU - Chen, Yen Cheng

AU - Lin, Shih Li

AU - Chen, Tzen-Wen

AU - Chen, Tso Hsiao

PY - 2009

Y1 - 2009

N2 - Urotensin-II (UII) is a potent vasoactive peptide that has been implicated in cardiac fibrosis and renal diseases. However, the role played by UII in renal tissues is largely unknown. In this study, we investigated the effects of human UII (hUII) on rat renal proximal tubular cells of the NRK-52E line and the role of Src homology 2-containing phosphotyrosine phosphatase (SHP-2) in the hUII-induced transactivation of the epidermal growth factor receptor (EGFR). Exposure to hUII at low concentrations significantly induced proliferation in NRK-52E cells; this effect was inhibited by treatment with an ERK1/2 inhibitor (PD98059). UII treatment increased the phosphorylation of EGFR and induced the generation of reactive oxygen species (ROS). Treatment of the ROS scavenger N-acetyl-cysteine (NAC) inhibited EGFR transactivation and ERK phosphorylation induced by hUII. SHP-2 was found to interact with EGFR and be transiently oxidized following the hUII treatment. In SHP-2 knockdown cells, UII-induced phosphorylation of EGFR was less influenced by NAC, and significantly suppressed by heparin binding (HB)-EGF neutralizing antibody. Our data suggest that the ROS-mediated oxidation of SHP-2 is essential for the hUII-induced mitogenic pathway in NRK-52E cells.

AB - Urotensin-II (UII) is a potent vasoactive peptide that has been implicated in cardiac fibrosis and renal diseases. However, the role played by UII in renal tissues is largely unknown. In this study, we investigated the effects of human UII (hUII) on rat renal proximal tubular cells of the NRK-52E line and the role of Src homology 2-containing phosphotyrosine phosphatase (SHP-2) in the hUII-induced transactivation of the epidermal growth factor receptor (EGFR). Exposure to hUII at low concentrations significantly induced proliferation in NRK-52E cells; this effect was inhibited by treatment with an ERK1/2 inhibitor (PD98059). UII treatment increased the phosphorylation of EGFR and induced the generation of reactive oxygen species (ROS). Treatment of the ROS scavenger N-acetyl-cysteine (NAC) inhibited EGFR transactivation and ERK phosphorylation induced by hUII. SHP-2 was found to interact with EGFR and be transiently oxidized following the hUII treatment. In SHP-2 knockdown cells, UII-induced phosphorylation of EGFR was less influenced by NAC, and significantly suppressed by heparin binding (HB)-EGF neutralizing antibody. Our data suggest that the ROS-mediated oxidation of SHP-2 is essential for the hUII-induced mitogenic pathway in NRK-52E cells.

KW - Epidermal growth factor receptor transactivation

KW - Rat renal proximal tubular cells

KW - Reactive oxygen species

KW - Src homology 2-containing phosphotyrosine phosphatase

KW - Urotensin II

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U2 - 10.1080/08977190902879866

DO - 10.1080/08977190902879866

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SP - 155

EP - 162

JO - Growth Factors

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SN - 0897-7194

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