PDK1调控小鼠心脏流出道发育形成并协同Nkx2.5调节房室轴形成的作用

Abstract
Figure/Table
References (25)
Related Citation (0)

Download: PDF (0 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To observe the effect of phosphoinositide-dependent protein kinase-1 (PDK1) in regulating development of cardiac outflow tract (OFT) and the synergetic effect with Nkx2.5 on artrioventricular canal (AVC) formation in mice. Methods Crossed PDK1F/F mouse with Nkx2.5-cre mouse, in the second progeny got the mice with PDK1F/+,PDK1+/+ and PDK1F/F three kinds of genotypes, in each type Nkx2.5-cre was positive or negative. After the genotype of mouse was confirmed by PCR, the phenotype of heart was analyzed, firstly the general appearance was observed under microscope and photos were taken, then the hearts were made into paraffin sections, the microstructure of hearts was observed under microscope after being dyed with HE. Results All the mice could survive to birth. The control mice PDK1F/F showed normal heart structure, however, PDK1F/F, Nkx2.5-cre mice all displayed prominent pulmonary stenosis,the phenotype included narrow vessel, non-division of pulmonary valve and aneurysm. And in one PDK1+/+ case, the heart developed into three cavities, two atriums and one ventricle without AVC being developed to separate the cavities.And in another PDK1F/+，Nkx2.5-cre case，the heart was developed into four cavities, two atriums and two ventricles, equally lacking AVC developed to divide the cavities, meanwhile, the OFT failed to separate. Considering Nkx2.5-cre mouse is a cre knock-in mouse, in which one Nkx2.5 allele is damaged, it is possible to cause heart malformation even though PDK1 isn′t knocked out completely. Conclusion PDK1 is an important factor which controls OFT development,and it probably cooperates with Nkx2.5 to regulate cardiac OFT, AVC development.

Key words： Phosphoinositide-dependent protein kinase-1 Nkx2.5 Outflow tract Artrioventricular canal Cardiogenesis

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	LUO Hongmei
	YANG Zhongzhou
	SHAN Congjia

Cite this article:

LUO Hongmei,YANG Zhongzhou,SHAN Congjia. Effect of PDK1 in regulating cardiac outflow tract development and the synergetic effect with Nkx2.5 on artrioventricular canal formation in mice[J]. 中国当代医药, 2022, 29(16): 30-34.

URL:

https://www.dangdaiyiyao.com/EN/ OR https://www.dangdaiyiyao.com/EN/Y2022/V29/I16/30

[1]	Li YW，Yang KJ，Park J.Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer[J].World J Biol Chem，2010，1（8）：239-247.
[2]	Park J，Hill MM，Hess D，et al.Identification of Tyrosine Phosphorylation Sites on 3-Phosphoinositide-dependent Protein Kinase-1 and Their Role in Regulating Kinase Activity[J].J Biol Chem，2001，276（40）：37459-37471.
[11]	Yamagishi H.Cardiac Neural Crest[J].Cold Spring Harb Perspect Biol，2021，13（1）：a036715.
[17]	Di RM，Feng QT，Chang Z，et al.PDK1 plays a critical role in regulating cardiac function in mice and human[J].Chin Med J,2010.123（17）：2358-2363.
[21]	吉晓理，罗江宾，冯旭霞.心脏发育相关基因NKX2.5 突变与三亚地区儿童先天性心脏病的相关性研究[J].中国优生与遗传杂志，2020，28（3）：309-310.
[3]	Lawlor MA，Mora A，Ashby P，et al.Essential role of PDK1 in regulating cell size and development in mice[J].EMBO J，2002，21（14）：3728-3738.
[4]	Feng QT，Di RM，Tao F，et al.PDK1 Regulates Vascular Remodeling and Promotes Epithelial-Mesenchymal Transition in Cardiac Development[J].Mol Cell Biol，2010，30（14）：3711-3721.
[5]	Jin HW，Wang HJ，Li J，et al.Differential contribution of the two waves of cardiac progenitors and their derivatives to aorta and pulmonary artery[J].Dev Biol，2019，450（7）：82-89.
[6]	Luo W，Zhao X，Jin HW，et al.Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development[J].Development，2015，142（4）：732-742.
[7]	Wang HS，Liu Y，Zi YF，et al.Nkx2-5 Regulates the Proliferation and Migration of H9c2 Cells[J].Med Sci Monit，2020，11（8）：1-16.
[8]	Dupays L，Towers N，Wood S，et al.Furin，a transcriptional target of NKX2-5，has an essential role in heart development and function[J].PLoS One，2019，6（3）：1-21.
[9]	Laurent F，Girdziusaite A，Gamart J，et al.HAND2 Target Gene Regulatory Networks Control Atrio-ventricular Canal and Cardiac Valve Development[J].Cell Rep，2017，19（8）：1602-1613.
[10]	Duchemin AL，Vignes H，Vermot J.Mechanically activated piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis[J].Elife，2019，16（9）：1-27.
[12]	Moses K，DeMayo F，Braun RM，et al.Embryonic expression of an Nkx2-5/cre gene using ROSA26 reporter mice[J].Genesis，2001，31（4）：176-180.
[13]	Zhao X，Lu SS，Nie JW，et al.Phosphoinositide-Dependent Kinase 1 and mTORC2 Synergistically Maintain Postnatal Heart Growth and Heart Function in Mice[J].Mol Cell Biol，2014，34（11）：1966-1975.
[14]	Biondi RM，komander D，thomas C，et al.High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory ohisphopeptide docking site[J].EMBO J，2002，21（16）：4219-4228.
[15]	Pende M，Um S.H，Mieulet V，et al.S6K1-/-，S6K2-/- Mice Exhibit Perinatal Lethality and Rapamycin-Sensitive 5-Terminal Oligopyrimidine mRNA Translation and Reveal a Mitogen-Activated Protein Kinase-Dependent S6 Kinase Pathway[J].Mol Cell Biol，2004，24（8）：3112-3124.
[22]	谢华斌，马芳芳.NKX2.5 基因63A＞G 多态性与先天性心脏病相关性的Meta 分析[J].中国优生与遗传杂志，2018，26（10）：17-20.
[23]	许展毓，冯旭，郑宝石，等.先天性心脏病与同源蛋白NKX2.5 基因突变的关系[J].中华实验外科杂志，2018，35（1）：149-152.
[24]	李倩，熊符，李承彬.中国南方单纯性先天性心脏病患者Nkx2.5 基因突变的研究[J].中国优生与遗传杂志，2017，25（9）：85-87.
[25]	江敏，梁燕华，林丽虹.转录因子Nkx2.5、GATA4 在先天性心脏病产前诊断中的研究[J].中国实用医药，2020，15（4）：196-198.
[16]	Mora A，Davies AM，Bertrand L，et al.Deficiency of PDK1 in cardiac muscle results in heart failure and increased sensitivity to hypoxia[J].EMBO J，2003，22（18）：4666-4676.
[18]	Lyons I，Parsons LM，Hartley L，et al.Myogenic and morphogenetic defects in the heart tubes of murine lacking the homeo box gene Nkx2.5[J].Genes Dev，1995，9：1654-1666.
[19]	Zhang L，Nomura-Kitabayashi A，Sultana N，et al.Nkx2.5 is necessary and sufficient for early second heart field development[J].Dev Biol，2014，390（2）：68-79.
[20]	Benson DW，Silberbach GM，McHugh AK，et al.Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways[J].J Clin Invest，1999，104（11）：1567-1573.