TY - JOUR
T1 - Caspase-3 regulates ureteric branching in mice via cell migration
AU - Awazu, Midori
AU - Yamaguchi, Yoshifumi
AU - Nagata, Michio
AU - Miura, Masayuki
AU - Hida, Mariko
N1 - Funding Information:
Supported by JSPS KAKENHI grant Number JP15K09726.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6/25
Y1 - 2021/6/25
N2 - 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.
AB - 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.
KW - Caspase-3
KW - Migration
KW - Nephron number
KW - Non-apoptotic
KW - Ureteric bud branching
UR - http://www.scopus.com/inward/record.url?scp=85107117402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107117402&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2021.04.081
DO - 10.1016/j.bbrc.2021.04.081
M3 - Article
C2 - 33932897
AN - SCOPUS:85107117402
SN - 0006-291X
VL - 559
SP - 28
EP - 34
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -