[1]傅明炜,王热华,林锋,等.SFRP1通过抑制Wnt/β-catenin通路促进心肌细胞增殖的分子机制[J].福建医药杂志,2022,44(06):117-120.
 Fu Mingwei,Wang Rehua,Lin Feng,et al.SFRP1 promotes cardiomyocyte proliferation via inhibiting the Wnt/β-catenin pathway[J].FUJIAN MEDICAL JOURNAL,2022,44(06):117-120.
点击复制

SFRP1通过抑制Wnt/β-catenin通路促进心肌细胞增殖的分子机制()
分享到:

《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
44
期数:
2022年06期
页码:
117-120
栏目:
基础研究
出版日期:
2022-12-15

文章信息/Info

Title:
SFRP1 promotes cardiomyocyte proliferation via inhibiting the Wnt/β-catenin pathway
文章编号:
1002-2600(2022)06-0117-04
作者:
傅明炜王热华林锋郭延松
福建医科大学省立临床医学院 福建省立医院心内科(福州 350001)
Author(s):
Fu MingweiWang RehuaLin FengGuo Yansong
Department of Cardiology,Fujian Provincial Hospital,Provincial Clinical College of Fujian Medical University,Fuzhou,Fujian 350001,China
关键词:
SFRP1Wnt/β-catenin心肌细胞细胞增殖
Keywords:
SFRP1 Wnt/β-catenincardiomyocytecell proliferation
分类号:
R541
文献标志码:
A
摘要:
目的 探讨SFRP1是否通过抑制Wnt/β-catenin通路促进心肌细胞增殖。方法 选取c57BL/6雄性小鼠18只,出生后1 d、7 d及28 d的c57BL/6小鼠各6只分为3组,分离和提取心肌组织,检测心肌组织中SFRP1的mRNA及蛋白表达水平。利用出生后1 d的乳鼠心脏培养小鼠原代心肌细胞,予SFRP1-shRNA慢病毒转染细胞,免疫荧光检测心肌细胞增殖标志物Ki67和PH3表达变化,Western blot检测胞浆β-catenin蛋白表达变化。结果 SFRP1 mRNA和蛋白水平在小鼠出生后逐渐下降(P<0.05)。转染SFRP1-shRNA慢病毒后,SFRP1蛋白表达水平均下降(P<0.05),其中shRNA-2干扰效果最好。与空载组相比,shRNA组细胞Ki67和PH3表达下降,同时胞浆β-catenin蛋白表达水平升高(P<0.05)。结论 SFRP1通过抑制Wnt/β-catenin信号通路促进心肌细胞增殖。
Abstract:
Objective To investigate whether SFRP1 promotes cardiomyocyte proliferation via inhibiting the Wnt/β-catenin pathway. Methods Six c57BL/6 mice were selected which were 1/7/28-day old, respectively. The myocardial tissue was isolated and extracted, and the mRNA and protein expression levels of SFRP1 in myocardial tissue were detected. Primary mouse cardiomyocytes were cultured and identified from 1-day-old mice. Cells were transfected with SFRP1-shRNA lentivirus or vector lentivirus, and the interference efficiency of shRNA was verified by WB, besides the shRNA with the best interference effect was selected for subsequent experiments. The expression of α -actinin and proliferation markers of cardiomyocytes (Ki67, PH3) were detected by immunofluorescence, and the expression of β-catenin protein in cytoplasm was detected by WB. Results The mRNA and protein expression of SFRP1 was highest in the myocardial tissue of mice which were 1-day old, and decreased gradually 7 and 28-day old. The primary cardiomyocytes of newborn mice were cultured successfully. The survival rate of cardiomyocytes was more than 95% by trypan blue staining, and α-actinin immunofluorescence staining showed that the purity of cardiomyocytes was more than 95%. Compared with the vector group, the expression levels of SFRP1 protein in SFRP1-shRNA lentivirus group were decreased (ALL P<0. 01), and the interference effect of shRNA-2 was the best. Compared to vector group, the expression of α-actinin, Ki67 and PH3 were decreased in shRNA group, and the expression of β-catenin protein in cytoplasm was increased (P<0. 01). Conclusion SFRP1 promotes cardiomyocyte proliferation via inhibiting the Wnt/β-catenin pathway.

参考文献/References:

[1] Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)[J]. Eur Heart J, 2018, 39(11):119-177.
[2] Bassat E, Mutlak Y E, Genzelinakh A, et al. The extracellular matrix protein agrin promotes heart regeneration in mice[J]. Nature, 2017, 547(7662):179-184.
[3] Wang W E, Li L, Xia X, Fu W, et al. Dedifferentiation, proliferation and redifferentiation of adult mammalian cardiomyocytes after ischemic injury[J]. Circulation, 2017, 136(9):834-848.
[4] Xie, S, Fu, W, Yu, G, et al. Discovering small molecules as Wnt inhibitors that promote heart regeneration and injury repair[J]. J Mol Cell Biol, 2020, 12(1):42-54.
[5] Tao J, Wei X, Huang Y, et al. Sfrp1 protects against acute myocardial ischemia (AMI) injury in aged mice by inhibiting the Wnt/β-catenin signaling pathway[J]. Journal of Cardiothoracic Surgery, 2021, 16(1):1-10.
[6] Gibb N, Lavery D L, Hoppler S. Sfrp1 promotes cardiomyocyte differentiation in xenopus via negative-feedback regulation of Wnt signalling[J]. Development, 2013, 140(7):1537-1549.
[7] Eschenhagen T, Bolli R, Braun T, et al. Cardiomyocyte regeneration: A consensus statement[J]. Circulation, 2017, 136(7):1-7.
[8] Bastakoty D, Saraswati S, Joshi P, et al. Temporary, systemic inhibition of the Wnt/β-catenin promotes regenerative cardiac repair following myocardial infarct[J]. Cell Stem Cells Regen Med, 2016, 2(2):1-27.
[9] Moon J, Zhou H, Zhang LS, et al. Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist[J]. PNAS, 2017, 114(7):1649-1654.
[10] Sklepkiewicz P, Shiomi T, Kaur R, et al. Loss of secreted frizzled-related protein-1 leads to deterioration of cardiac function in mice and plays a role in human cardiomyopathy[J]. Circ Heart Fail, 2015, 8(2):362-372.
[11] Bergmann M W. WNT signaling in adult cardiac hypertrophy and remodeling: lessons learned from cardiac development[J]. Circ Res, 2010, 107(10):1198-208.
[12] Zelarayán L C, Noack C, Sekkali B, et al. Beta-Catenin downregulation attenuates ischemic cardiac remodeling through enhanced resident precursor cell differentiation[J]. PNAS, 2008, 105(50):19762-19767.

相似文献/References:

[1]周子杰,张家豪,姜吉霖,等.miR-586通过SFRP1调控骨肉瘤细胞增殖、迁移、侵袭的机制研究[J].福建医药杂志,2024,46(01):115.[doi:10.20148/j.fmj.2024.01.032]

备注/Memo

备注/Memo:
基金项目:福建省卫生健康科研人才培养项目(2019-1-8)
更新日期/Last Update: 2022-12-15