ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice
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概要
- 論文の詳細を見る
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.
- 日本組織細胞化学会の論文
著者
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Nishida Masashi
Department Of Applied Chemistry Faculty Of Engineering Sojo University
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Hamaoka Kenji
Department Of Pediatric Cardiology And Nephrology
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Kohno Michiaki
Department Of Cell Reguration Faculty Of Pharmacology Nagasaki University
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Sugiyama Noriyuki
Department Of Anatomy And Developmental Biology Graduate School Of Medical Science Kyoto Prefectural
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Tanimura Susumu
Department Of Biology Konan University
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Yokoyama Takahiko
Department Of Anatomy And Developmental Biology Graduate School Of Medical Science Kyoto Prefectural
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Okumura Yasuko
Department Of Anatomy And Developmental Biology Graduate School Of Medical Science Kyoto Prefectural University Of Medicine
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Kohno Michiaki
Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University
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Nishida Masashi
Department of Pediatric Cardiology and Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine
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Okumura Yasuko
Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine
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Tanimura Susumu
Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University
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