Cyclic stretch induces proliferation and TGF-β1-mediated apoptosis via p38 and ERK in ureteric bud cells

Hisayo Fujita, Mariko Hida, Katsuyoshi Kanemoto, Keiichi Fukuda, Michio Nagata, Midori Awazu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

We previously reported that p38 mitogen-activated protein kinase (p38) and phosphorylated ERK are upregulated in cyst epithelium of human renal dysplasia and obstructive uropathy in fetal lambs (Omori S, Fukuzawa R, Hida M, Awazu M. Kidney Int 61: 899-906, 2002; Omori S, Kitagawa H, Koike J, Fujita H, Hida M, Pringle KC, Awazu M. Kidney Int 73: 1031-1037, 2008). Dysplastic epithelium is characterized by proliferation, apoptosis, and upregulation of Pax2 and transforming growth factor (TGF)-β1. In the present study, we investigated whether cyclic mechanical stretching of ureteric bud cells, a mimic of the hydrodynamic derangement after fetal urinary tract obstruction, reproduces events seen in vivo. Cyclic stretch activated p38 and ERK and upregulated Pax2 expression in a time-dependent manner in ureteric bud cells. Stretch-stimulated Pax2 expression was suppressed by a p38 inhibitor, SB203580, or a MEK inhibitor, PD98059. 5-Deoxyuridine incorporation was increased by stretch at 24 h, which was also abolished by SB203580 or PD98059. On the other hand, apoptosis was not induced at 24 h by stretch but was significantly increased at 48 h. TGF-β1 secretion was increased by stretch at 24 h, which was inhibited by SB203580 or PD98059. Inhibition of p38 or ERK as well as anti-TGF-β antibody abolished the stretch-induced apoptosis. Finally, exogenous TGF-β1 induced apoptosis of ureteric bud cells, which was inhibited by SB203580 and PD98059. In conclusion, cyclic stretch induces Pax2 upregulation, proliferation, and TGF-β1-mediated apoptosis, features characteristic of dysplastic epithelium, via p38 and ERK in ureteric bud cells.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume299
Issue number3
DOIs
Publication statusPublished - 2010 Sep

Fingerprint

Transforming Growth Factors
Apoptosis
Epithelium
p38 Mitogen-Activated Protein Kinases
Kidney
Up-Regulation
Deoxyuridine
Mitogen-Activated Protein Kinase Kinases
Hydrodynamics
Urinary Tract
Cysts
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Antibodies

Keywords

  • Cell signaling
  • Dysplastic kidney
  • Kidney development
  • Obstructive uropathy

ASJC Scopus subject areas

  • Physiology
  • Urology
  • Medicine(all)

Cite this

Cyclic stretch induces proliferation and TGF-β1-mediated apoptosis via p38 and ERK in ureteric bud cells. / Fujita, Hisayo; Hida, Mariko; Kanemoto, Katsuyoshi; Fukuda, Keiichi; Nagata, Michio; Awazu, Midori.

In: American Journal of Physiology - Renal Physiology, Vol. 299, No. 3, 09.2010.

Research output: Contribution to journalArticle

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AU - Nagata, Michio

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