Caspase-3 regulates ureteric branching in mice via cell migration
Caspase-3 regulates ureteric branching in mice via cell migration
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Caspase-3通过细胞迁移调节小鼠输尿管分支
DOI：
10.1016/j.bbrc.2021.04.081
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发表时间：
2021
影响因子：
3.1
通讯作者：
Hida Mariko
中科院分区：
文献类型：
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作者：
Awazu Midori;Yamaguchi Yoshifumi;Nagata Michio;Miura Masayuki;Hida Mariko
抑制胱天蛋白酶-3（Casp 3）可减少器官培养中的输尿管分支，但其机制尚不清楚。由于Casp 3具有非凋亡功能，我们使用输尿管芽（UB）细胞系和Casp 3缺陷（Casp 3 −/−）小鼠研究了Casp 3是否通过促进细胞迁移来调节输尿管分支。此外，我们还研究了Casp 3是否在营养限制的母亲的后肾输尿管分支减少中发挥作用，其中Casp 3活性受到抑制。在3D培养中，Casp 3抑制剂Ac-DNLD-CHO减少了FGF 2诱导的UB细胞索形成。通过Boyden室和伤口愈合试验评估的UB细胞迁移被Ac-DNLD-CHO抑制。与对照组相比，Casp 3 −/−小鼠的肾小球数量减少了约30%，输尿管尖端数量减少。母体营养限制减少对照组的输尿管尖端数量，但在Casp 3 −/−中没有。总之，Casp 3通过促进UB细胞迁移调节输尿管分支。母体营养限制抑制输尿管分支可能是由Casp 3介导的。
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.