ERK and p38 mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells

Hisayo Fujita, Sayu Omori, Kenji Ishikura, Mariko Hida, Midori Awazu

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 And phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. Transforming growth factor (TGF)-β was expressed in all tubular segments of DM, coinciding with the localization of p38. In LLC-PK1 cells, phosphorylation of ERK and p38 increased after 24- to 72-h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [3H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-β protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF-β expression.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number1 55-1
Publication statusPublished - 2004 Jan

Fingerprint

Transforming Growth Factors
Hypertrophy
Kidney
Glucose
p38 Mitogen-Activated Protein Kinases
LLC-PK1 Cells
Proteins
Mitogen-Activated Protein Kinase Kinases
Streptozocin
Leucine
Phosphorylation
Injections
DNA
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Keywords

  • Diabetes
  • Kidney
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Physiology

Cite this

ERK and p38 mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells. / Fujita, Hisayo; Omori, Sayu; Ishikura, Kenji; Hida, Mariko; Awazu, Midori.

In: American Journal of Physiology - Renal Physiology, Vol. 286, No. 1 55-1, 01.2004.

Research output: Contribution to journalArticle

@article{2559af8391ed45e8844834fe05bc3936,
title = "ERK and p38 mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells",
abstract = "We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 And phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. Transforming growth factor (TGF)-β was expressed in all tubular segments of DM, coinciding with the localization of p38. In LLC-PK1 cells, phosphorylation of ERK and p38 increased after 24- to 72-h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [3H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-β protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF-β expression.",
keywords = "Diabetes, Kidney, Mitogen-activated protein kinase",
author = "Hisayo Fujita and Sayu Omori and Kenji Ishikura and Mariko Hida and Midori Awazu",
year = "2004",
month = "1",
language = "English",
volume = "286",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1 55-1",

}

TY - JOUR

T1 - ERK and p38 mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells

AU - Fujita, Hisayo

AU - Omori, Sayu

AU - Ishikura, Kenji

AU - Hida, Mariko

AU - Awazu, Midori

PY - 2004/1

Y1 - 2004/1

N2 - We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 And phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. Transforming growth factor (TGF)-β was expressed in all tubular segments of DM, coinciding with the localization of p38. In LLC-PK1 cells, phosphorylation of ERK and p38 increased after 24- to 72-h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [3H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-β protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF-β expression.

AB - We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 And phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. Transforming growth factor (TGF)-β was expressed in all tubular segments of DM, coinciding with the localization of p38. In LLC-PK1 cells, phosphorylation of ERK and p38 increased after 24- to 72-h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [3H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-β protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF-β expression.

KW - Diabetes

KW - Kidney

KW - Mitogen-activated protein kinase

UR - http://www.scopus.com/inward/record.url?scp=0347360288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347360288&partnerID=8YFLogxK

M3 - Article

C2 - 12952860

AN - SCOPUS:0347360288

VL - 286

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1 55-1

ER -