Caspase-3 regulates ureteric branching in mice via cell migration.

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

Biochemical and biophysical research communications 2021 Jun 25

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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. Copyright © 2021 Elsevier Inc. All rights reserved.

Citation

Midori Awazu, Yoshifumi Yamaguchi, Michio Nagata, Masayuki Miura, Mariko Hida. Caspase-3 regulates ureteric branching in mice via cell migration. Biochemical and biophysical research communications. 2021 Jun 25;559:28-34