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

研究成果: Article査読

16 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)F648-F655
ジャーナルAmerican Journal of Physiology - Renal Physiology
299
3
DOI
出版ステータスPublished - 2010 9月 1

ASJC Scopus subject areas

  • 生理学
  • 泌尿器学

フィンガープリント

「Cyclic stretch induces proliferation and TGF-β1-mediated apoptosis via p38 and ERK in ureteric bud cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル