Leupaxin is upregulated in fibrotic kidneys and contributes to the proliferation of kidney fibroblasts

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  • Noda Shunsuke
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Obana Masanori
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University
  • Miyake Yoshiaki
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Yamamoto Ayaha
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Tanaka Shota
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Maeda Makiko
    Laboratory of Clinical Pharmacology and Therapeutics, Grad. Sch. Pharm., Osaka Univ.
  • Okada Yoshiaki
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University
  • Fujio Yasushi
    Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical sciences, Osaka University Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University

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Other Title
  • 腎線維化時に発現上昇するleupaxinは腎線維芽細胞の増殖を制御する

Abstract

<p>[Introduction]</p><p>Fibrosis is the final common pathway of chronic kidney disease, leading to end-stage renal failure. In our previous data, the transcript expression of leupaxin, a member of paxillin protein family, was upregulated in the fibrotic kidneys, analyzed by microarray. However, the role of leupaxin in kidney fibrosis is unclear. The aim of this study is to assess the function of leupaxin in kidney fibroblasts which play critical roles in kidney fibrosis.</p><p>[Methods and Results]</p><p>Kidney fibrosis model was generated by ligating the unilateral ureter of C57Bl/6J mice (UUO). Quantitative PCR analysis showed that leupaxin mRNA expression was increased 1, 3 and 7 days after UUO. Moreover, immunohistochemical staining revealed that leupaxin was expressed in the fibrotic area 7 days after UUO. Next, we explored the function of leupaxin in fibroblasts using cultured rat renal fibroblasts NRK49F cells. Immunostaining and western blotting demonstrated that leupaxin localized in the cell nuclei. Finally, The knock-down of leupaxin by lentiviral shRNA resulted in the reduced proliferative capacity of NRK49F cells.</p><p>[Conclusion]</p><p>Leupaxin regulates the proliferation of kidney fibroblasts as a nuclear protein. The suppression of leupaxin could be a therapeutic approach for kidney fibrosis.</p>

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