Caspase-3 regulates ureteric branching in mice via cell migration

Midori Awazu, Yoshifumi Yamaguchi, Michio Nagata, Masayuki Miura, Mariko Hida

Research output: Contribution to journalArticlepeer-review

Abstract

Inhibition of caspase-3 (Casp3) reduces ureteric branching in organ culture but the mechanism remains unclear. Since Casp3 has non-apoptotic functions, we examined whether Casp3 regulates ureteric branching by promoting cell migration, using a ureteric bud (UB) cell line and Casp3-deficient (Casp3−/−) mice. Also, we examined whether Casp3 plays a role in the reduced ureteric branching of metanephroi from nutrient restricted mothers, in which Casp3 activity is suppressed. A Casp3 inhibitor Ac-DNLD-CHO reduced FGF2-induced cord formation of UB cells in 3D culture. UB cell migration assessed by Boyden chamber and wound healing assays was inhibited by Ac-DNLD-CHO. Glomerular number was reduced by ≈ 30%, and ureteric tip number was lower in Casp3−/− mice compared with controls. Maternal nutrient restriction decreased ureteric tip number in controls but not in Casp3−/−. In conclusion, Casp3 regulates ureteric branching by promoting UB cell migration. Inhibited ureteric branching by maternal nutrient restriction may be mediated by Casp3.

Original languageEnglish
Pages (from-to)28-34
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume559
DOIs
Publication statusPublished - 2021 Jun 25
Externally publishedYes

Keywords

  • Caspase-3
  • Migration
  • Nephron number
  • Non-apoptotic
  • Ureteric bud branching

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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