Basic helix-loop-helix transcriptional factor MyoR regulates BMP-7 in acute kidney injury

Nozomu Kamiura, Junichi Hirahashi, Yumi Matsuzaki, Mana Idei, Osamu Takase, Toshiro Fujita, Tsuyoshi Takato, Keiichi Hishikawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

MyoR was originally identified as a transcriptional repressor in embryonic skeletal muscle precursors, but its function in adult kidney has not been clarified. In this study, we tried to clarify the functional role of MyoR using MyoR-/- mice. Cisplatin induced a significantly higher degree of severe renal dysfunction, tubular injury, and mortality in MyoR-/- mice than in wild-type mice. The injection of cisplatin significantly increased the number of apoptotic cells in the kidney tissues of MyoR-/- mice, compared with that in wild-type mice. To clarify the mechanism of severe cisplatin-induced damage and apoptosis in MyoR-/- mice, we focused on the p53 signaling pathway and bone morphogenic protein-7 (BMP-7). Treatment with cisplatin significantly activated p53 signaling in cultured renal proximal tubular epithelial cells (RTECs) in both wild-type and MyoR-/- mice, but no significant difference between the groups was observed. The injection of cisplatin significantly increased the expression of BMP-7 in the kidney tissues of wild-type mice, but no increase was observed in the MyoR-/- mice. Treatment with cisplatin significantly increased the expression of BMP-7 in cultured RTECs from wild-type mice but not in those from MyoR-/- mice. Moreover, treatment with recombinant BMP-7 rescued the cisplatin-induced apoptosis in RTECs from MyoR-/- mice. Taken together, our results demonstrate a new protective role of MyoR in adult kidneys that acts through the regulation of BMP-7.

Original languageEnglish
Pages (from-to)F1159-F1166
JournalAmerican Journal of Physiology - Renal Physiology
Volume304
Issue number9
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • AKI
  • BMP-7
  • Stem cell

ASJC Scopus subject areas

  • Physiology
  • Urology

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