title: ERK regulates renal cell proliferation and renal cyst expansion in inv mutant mice.
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 invDeltaC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invDeltaC 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.
authors.affiliation: Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Okumura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Susumu
authors.initials: S
authors.lastname: Tanimura
authors.forename: Masashi
authors.initials: M
authors.lastname: Nishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamaoka
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kohno
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yokoyama