ERK and p38 MAP kinase are required for rat renal development

Mariko Hida, Sayu Omori, Midori Awazu

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Background. We previously demonstrated that extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase (p38) are strongly expressed in the embryonic kidney. In the present study, we investigated the role of ERK and p38 during kidney development. Methods. Rat metanephroi were cultured from 15-day-old embryos, and exposed to inhibitors of MEK, an activator of ERK, PD98059 (300 μmol/L), U0126 (10 μmol/L), or a p38 inhibitor SB203580 (30 μmol/L) 24 to 120 hours after the start of culture. Growth of metanephroi was measured by surface area and thymidine incorporation. Ureteric buds and glomeruli were identified by labeling with Dolichos biflorus lectin and peanut agglutinin, respectively. PCNA staining and TUNEL assay were performed on kidney sections. The level of apoptosis was evaluated by examining DNA ladder formation. Results. Growth of metanephroi was significantly inhibited by SB203580 but not by PD98059 or U0126. Ureteric bud branching was not affected by SB203580 or MEK inhibitors. Glomerular number was markedly reduced by SB203580 and to a lesser extent by U0126 (14 ± 2 and 48 ± 10% of controls, respectively). On histological examination, the number of tubulo-glomerular structures was reduced in MEK inhibitor-treated metanephroi compared to controls. Very few mesenchymal condensates were observed in kidneys incubated with SB203580. PCNA-positive cells were reduced in SB203580-treated metanephroi compared to control and PD98059-treated kidneys. Apoptosis was increased in SB203580-treated kidneys and to a lesser extent in PD98059-treated cultures. Conclusions. Both ERK and p38 are required for renal development. ERK appears to play a role in nephrogenesis and p38 for kidney growth and nephrogenesis.

Original languageEnglish
Pages (from-to)1252-1262
Number of pages11
JournalKidney International
Volume61
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

p38 Mitogen-Activated Protein Kinases
Kidney
Mitogen-Activated Protein Kinase Kinases
Proliferating Cell Nuclear Antigen
Growth
Apoptosis
Peanut Agglutinin
Extracellular Signal-Regulated MAP Kinases
In Situ Nick-End Labeling
SB 203580
Thymidine
Protein Kinases
Embryonic Structures
Staining and Labeling
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
DNA
U 0126

Keywords

  • Extracellular signal-regulated protein kinase
  • Kidney
  • Mitogen-activated protein kinase
  • Nephrogenesis
  • p38 mitogen-activated protein kinase
  • Ureteric bud

ASJC Scopus subject areas

  • Nephrology

Cite this

ERK and p38 MAP kinase are required for rat renal development. / Hida, Mariko; Omori, Sayu; Awazu, Midori.

In: Kidney International, Vol. 61, No. 4, 2002, p. 1252-1262.

Research output: Contribution to journalArticle

Hida, Mariko ; Omori, Sayu ; Awazu, Midori. / ERK and p38 MAP kinase are required for rat renal development. In: Kidney International. 2002 ; Vol. 61, No. 4. pp. 1252-1262.
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AU - Hida, Mariko

AU - Omori, Sayu

AU - Awazu, Midori

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N2 - Background. We previously demonstrated that extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase (p38) are strongly expressed in the embryonic kidney. In the present study, we investigated the role of ERK and p38 during kidney development. Methods. Rat metanephroi were cultured from 15-day-old embryos, and exposed to inhibitors of MEK, an activator of ERK, PD98059 (300 μmol/L), U0126 (10 μmol/L), or a p38 inhibitor SB203580 (30 μmol/L) 24 to 120 hours after the start of culture. Growth of metanephroi was measured by surface area and thymidine incorporation. Ureteric buds and glomeruli were identified by labeling with Dolichos biflorus lectin and peanut agglutinin, respectively. PCNA staining and TUNEL assay were performed on kidney sections. The level of apoptosis was evaluated by examining DNA ladder formation. Results. Growth of metanephroi was significantly inhibited by SB203580 but not by PD98059 or U0126. Ureteric bud branching was not affected by SB203580 or MEK inhibitors. Glomerular number was markedly reduced by SB203580 and to a lesser extent by U0126 (14 ± 2 and 48 ± 10% of controls, respectively). On histological examination, the number of tubulo-glomerular structures was reduced in MEK inhibitor-treated metanephroi compared to controls. Very few mesenchymal condensates were observed in kidneys incubated with SB203580. PCNA-positive cells were reduced in SB203580-treated metanephroi compared to control and PD98059-treated kidneys. Apoptosis was increased in SB203580-treated kidneys and to a lesser extent in PD98059-treated cultures. Conclusions. Both ERK and p38 are required for renal development. ERK appears to play a role in nephrogenesis and p38 for kidney growth and nephrogenesis.

AB - Background. We previously demonstrated that extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase (p38) are strongly expressed in the embryonic kidney. In the present study, we investigated the role of ERK and p38 during kidney development. Methods. Rat metanephroi were cultured from 15-day-old embryos, and exposed to inhibitors of MEK, an activator of ERK, PD98059 (300 μmol/L), U0126 (10 μmol/L), or a p38 inhibitor SB203580 (30 μmol/L) 24 to 120 hours after the start of culture. Growth of metanephroi was measured by surface area and thymidine incorporation. Ureteric buds and glomeruli were identified by labeling with Dolichos biflorus lectin and peanut agglutinin, respectively. PCNA staining and TUNEL assay were performed on kidney sections. The level of apoptosis was evaluated by examining DNA ladder formation. Results. Growth of metanephroi was significantly inhibited by SB203580 but not by PD98059 or U0126. Ureteric bud branching was not affected by SB203580 or MEK inhibitors. Glomerular number was markedly reduced by SB203580 and to a lesser extent by U0126 (14 ± 2 and 48 ± 10% of controls, respectively). On histological examination, the number of tubulo-glomerular structures was reduced in MEK inhibitor-treated metanephroi compared to controls. Very few mesenchymal condensates were observed in kidneys incubated with SB203580. PCNA-positive cells were reduced in SB203580-treated metanephroi compared to control and PD98059-treated kidneys. Apoptosis was increased in SB203580-treated kidneys and to a lesser extent in PD98059-treated cultures. Conclusions. Both ERK and p38 are required for renal development. ERK appears to play a role in nephrogenesis and p38 for kidney growth and nephrogenesis.

KW - Extracellular signal-regulated protein kinase

KW - Kidney

KW - Mitogen-activated protein kinase

KW - Nephrogenesis

KW - p38 mitogen-activated protein kinase

KW - Ureteric bud

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