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Intracellular localization of protein C inhibitor (PCI) and urinary plasminogen activator in renal tubular epithelial cells from humans and human PCI gene transgenic mice

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Abstract

Urinary plasminogen activator (uPA) is a serine protease that plays important roles in various extracellular proteolytic processes. In humans, protein C inhibitor (PCI) is known to regulate the activity of the serine proteases involved in blood coagulation, wound healing, and tumor metastasis, whereas PCI is not present in murine plasma or tissues other than the reproductive tissues. The large amount of uPA–PCI complexes found in human urine suggests that these complexes are formed in the kidneys. In the present study, we performed immunofluorescence double labeling and electron microscopic immunocytochemistry using renal tissues from humans and human PCI gene transgenic (PCI-TG) mice. In human renal tissues, PCI and uPA colocalized in the cytoplasm of renal proximal tubular epithelial cells (RPTECs), and juxtaposition of PCI and uPA immunoreactive particles was detected in the microvilli and lysosomes in the RPTECs. The intracellular distributions of PCI and uPA in the RPTECs from PCI-TG mice were similar to those observed in human RPTECs. These findings hint at the physiological roles of uPA and PCI in human kidneys, and also suggest that the PCI-TG mice will be useful for evaluating the roles of PCI in human physiological and pathological conditions.

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Abbreviations

PCI:

Protein C inhibitor

uPA:

Urinary plasminogen activator

RPTECs:

Renal proximal tubular epithelial cells

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Acknowledgments

This study was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (JSPS) (No. 17390276, 19390262), and a grant from the Mie University COE Project Fund.

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Authors and Affiliations

  1. Department of Molecular Pathobiology, Mie University Graduate School of Medicine, Tsu-city, Mie, 514-8507, Japan

    Zhenhu Song, Tatsuya Hayashi, Esteban C. Gabazza & Koji Suzuki

  2. Department of Anatomy, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan

    Ning Ma

  3. Department of Urology, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan

    Yoshiki Sugimura

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  1. Zhenhu Song
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  2. Ning Ma
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  3. Tatsuya Hayashi
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  5. Yoshiki Sugimura
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  6. Koji Suzuki
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Correspondence to Koji Suzuki.

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Song, Z., Ma, N., Hayashi, T. et al. Intracellular localization of protein C inhibitor (PCI) and urinary plasminogen activator in renal tubular epithelial cells from humans and human PCI gene transgenic mice. Histochem Cell Biol 128, 293–300 (2007). https://doi.org/10.1007/s00418-007-0330-6

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