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体外和体内血管生成中磷酸烯醇丙酮酸羧激酶1的需求

The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.

作者信息

Yao Jin, Wu Xin-Yuan, Yu Qing, Yang Shuo-Fei, Yuan Jin, Zhang Zhi-Qing, Xue Jin-Song, Jiang Qin, Chen Min-Bin, Xue Guan-Hua, Cao Cong

机构信息

The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.

Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

出版信息

Sci Adv. 2022 May 27;8(21):eabn6928. doi: 10.1126/sciadv.abn6928.

DOI:10.1126/sciadv.abn6928
PMID:35622925
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9140980/
Abstract

We here examined the potential biological function of phosphoenolpyruvate carboxykinase 1 (PCK1) in angiogenesis. shRNA- or CRISPR-Cas9-induced PCK1 depletion potently inhibited endothelial cell proliferation, migration, sprouting, and tube formation, whereas ectopic PCK1 overexpression exerted opposite activity. In HUVECs, Gα expression and Akt activation were decreased following PCK1 depletion, but were augmented by ectopic PCK1 overexpression. In vivo, retinal expression of PCK1 gradually increased from postnatal day 1 (P1) to P5. The intravitreous injection of endothelial-specific PCK1 shRNA adenovirus at P1 potently inhibited the radial extension of vascular plexus at P5. Conditional endothelial knockdown of PCK1 in adult mouse retina increased vascular leakage and the number of acellular capillaries while decreasing the number of RGCs in murine retinas. In diabetic retinopathy patients, mRNA and protein levels were up-regulated in retinal tissues. Together, PCK1 is essential for angiogenesis possibly by mediating Gα expression and Akt activation.

摘要

我们在此研究了磷酸烯醇式丙酮酸羧激酶1（PCK1）在血管生成中的潜在生物学功能。shRNA或CRISPR-Cas9诱导的PCK1缺失可有效抑制内皮细胞增殖、迁移、芽生和管腔形成，而异位PCK1过表达则发挥相反作用。在人脐静脉内皮细胞（HUVECs）中，PCK1缺失后Gα表达和Akt激活减少，但异位PCK1过表达则使其增强。在体内，PCK1的视网膜表达从出生后第1天（P1）到P5逐渐增加。在P1玻璃体腔内注射内皮特异性PCK1 shRNA腺病毒可有效抑制P5时血管丛的径向延伸。成年小鼠视网膜中PCK1的条件性内皮敲低增加了血管渗漏和无细胞毛细血管数量，同时减少了小鼠视网膜中视网膜神经节细胞（RGCs）的数量。在糖尿病视网膜病变患者中，视网膜组织中的mRNA和蛋白质水平上调。总之，PCK1可能通过介导Gα表达和Akt激活对血管生成至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/771d395ac350/sciadv.abn6928-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/21cd5990a532/sciadv.abn6928-f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/417636db13d4/sciadv.abn6928-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/771d395ac350/sciadv.abn6928-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/9545049715e6/sciadv.abn6928-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/262518617c4a/sciadv.abn6928-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/9308d443cd93/sciadv.abn6928-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/6471218fd7a9/sciadv.abn6928-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/21cd5990a532/sciadv.abn6928-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/0fafabbcf874/sciadv.abn6928-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/417636db13d4/sciadv.abn6928-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6376/9140980/771d395ac350/sciadv.abn6928-f8.jpg

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