ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

• Okumura Yasuko

  Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

• Sugiyama Noriyuki

  Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine

• Tanimura Susumu

  Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University

• Nishida Masashi

  Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

• Hamaoka Kenji

  Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine

• Kohno Michiaki

  Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University

• Yokoyama Takahiko

  Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine

Abstract

Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants.<br>

Journal

• ACTA HISTOCHEMICA ET CYTOCHEMICA

  ACTA HISTOCHEMICA ET CYTOCHEMICA 42 (2), 39-45, 2009

  JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY

Keywords

• ERK
• <i>inv</i>
• renal cyst
• cell proliferation
• MEK inhibitor

Details

• CRID: 1390282679839135744
• NII Article ID: 130000114963
• DOI: 10.1267/ahc.08040
• ISSN: 13475800
• ISSN: 00445991
• Web Site: http://www.jstage.jst.go.jp/article/ahc/42/2/42_08040/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2010041129
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed