Atypical protein kinase C is essential for embryonic vascular development in mice.
Atypical protein kinase C is essential for embryonic vascular development in mice.
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非典型蛋白激酶C对小鼠胚胎血管发育至关重要。
DOI：
10.1002/dvg.23412
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Ouyang K
中科院分区：
文献类型：
--
作者：
Chen Z;Duan Y;Wang H;Tang H;Wang S;Wang X;Liu J;Fang X;Ouyang K
非典型蛋白激酶C亚家族包括蛋白激酶Cζ和蛋白激酶Cλ，这两种蛋白激酶C亚型都参与了多种内皮细胞功能的调节。然而，aPKC在ECs胚胎发育过程中的生理功能还不是很清楚。为了解决这个问题，我们利用Tie2-Cre来缺失内皮细胞中的PKCλ(PKCλ-sko)或PKCλ和PKcζ(Dko)，发现所有dko小鼠在胚胎11.5天(E11.5)左右死亡，而PKCλ-sko小鼠存活到出生。在E10.5和E11.5，PKCλ-SKO胚胎的表型严重程度也低于DKO胚胎，提示PKCζ对胚胎内皮细胞中PKCλ具有潜在的代偿作用。然后，我们以DKO胚胎为研究对象，研究了aPKC缺陷对胚胎血管发育的影响。在E9.5，两种aPKC亚型的缺失使卵黄囊内的卵黄动、静脉管径减小，卵黄囊内两条卵黄血管的分支减少。同时，去除这两种aPKC亚型也破坏了胚胎头部和躯干的血管生成，增加了内皮细胞和非内皮细胞的凋亡。综上所述，我们的结果表明，内皮细胞中的aPKC在调节细胞凋亡、血管生成和胚胎存活方面发挥着重要作用。
The atypical PKC (aPKC) subfamily constitutes PKCζ and PKCλ in mice, and both aPKC isoforms have been proposed to be involved in regulating various endothelial cell (EC) functions. However, the physiological function of aPKC in ECs during embryonic development has not been well understood. To address this question, we utilized Tie2-Cre to delete PKCλ alone (PKCλ-SKO) or both PKCλ and PKCζ (DKO) in ECs, and found that all DKO mice died at around the embryonic day 11.5 (E11.5), whereas a small proportion of PKCλ-SKO mice survived till birth. PKCλ-SKO embryos also exhibited less phenotypic severity than DKO embryos at E10.5 and E11.5, suggesting a potential compensatory role of PKCζ for PKCλ in embryonic ECs. We then focused on DKO embryos and investigated the effects of aPKC deficiency on embryonic vascular development. At E9.5, deletion of both aPKC isoforms reduced the diameters of vitelline artery and vein, and decreased branching from both vitelline vessels in yolk sac. Ablation of both aPKC isoforms also disrupted embryonic angiogenesis in head and trunk at the same stage, increasing apoptosis of both ECs and non-ECs. Taken together, our results demonstrated that aPKC in ECs plays an essential role in regulating cell apoptosis, angiogenesis, and embryonic survival.
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影响因子：
20.1
作者：
Javaid, K;Rahman, A;Malik, AB
通讯作者：
Malik, AB
影响因子：
--
作者：
Hapak, Sophie M;Rothlin, Carla V;Ghosh, Sourav
通讯作者：
Ghosh, Sourav
影响因子：
4.8
作者：
Jani, Tanvi S.;DeVecchio, Jennifer;Houghton, Janet A.
通讯作者：
Houghton, Janet A.
DOI：
10.1083/jcb.201010051
发表时间：
2011-05-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Heo KS;Lee H;Nigro P;Thomas T;Le NT;Chang E;McClain C;Reinhart-King CA;King MR;Berk BC;Fujiwara K;Woo CH;Abe J
通讯作者：
Abe J
影响因子：
158.5
作者：
Dave, Sandeep S.;Fu, Kai;Staudt, Louis M.
通讯作者：
Staudt, Louis M.