HGF/c-Met信号通路与小鼠早期卵泡发育的相关性研究

doi:10.3969/j.issn.1006-5725.2023.20.002

实用医学杂志 ›› 2023, Vol. 39 ›› Issue (20): 2566-2571.doi: 10.3969/j.issn.1006-5725.2023.20.002

HGF/c-Met信号通路与小鼠早期卵泡发育的相关性研究

黎明星^1,²,李卓娴¹,李康梅¹,陈秀榕¹,周艳平¹,黄愉淋^1,²,白琳¹,吴展帅^1,²,夏猛¹,何国珍¹()

^1.广西中医药大学基础医学院（南宁 530200 ）
^2.广西高发传染病中西医结合转化医学重点实验室（南宁 530200 ）

收稿日期:2023-02-17 出版日期:2023-10-25 发布日期:2023-11-15
通讯作者: 何国珍 E-mail:1040550458@qq.com
基金资助:
国家自然科学基金项目(81960794);广西自然科学基金项目(2020GXNSFBA159064);广西中青年教师科研基础能力提升项目(2019KY0320);广西中医药大学引进博士科研启动基金项目(2018BS007);广西中医药大学高层次人才培育创新团队资助项目(2022B006);广西中医药大学第二批“岐黄工程”高层次人才团队培育项目(2021001);广西中医药大学大学生创新创业训练计划项目(S202110600092);广西中医药大学大学生科研训练课题(2022DXS04)

Role of hepatocyte growth factor （HGF）/c⁃Met signaling pathway in early follicular development in mice

Mingxing LI^1,²,Zhuoxian LI¹,Kangmei LI¹,Xiurong CHEN¹,Yanping ZHOU¹,Yulin HUANG^1,²,Lin BAI¹,Zhanshuai WU^1,²,Meng XIA¹,Guozhen. HE¹()

^1.Basic Medical College，Guangxi University of Chinese Medicine，Nanning 530200，China
^2.Guangxi Key Laboratory of Translational Medicine for Treating High?Incidence Infectious Diseases with Integrative Medicine，Nanning 530200，China

Received:2023-02-17 Online:2023-10-25 Published:2023-11-15
Contact: Guozhen. HE E-mail:1040550458@qq.com

摘要/Abstract

摘要：

目的通过检测肝细胞生长因子（HGF）及其受体（c-Met）在早期小鼠卵巢组织的表达情况，探讨HGF/c-Met信号通路在小鼠早期卵泡发育的相关性，并通过生物信息学分析HGF/c-Met通路的生物学过程及涉及的细胞内信号通路，为后续研究HGF/c-Met通路调节早期卵泡发育的分子机制打下基础。方法选用昆明小鼠以雌∶雄（2∶1）合笼，收集生后3、7、14、21 d卵巢，采用免疫组学、蛋白免疫印迹分别检测卵巢HGF和c-Met蛋白表达及表达水平；实时荧光定量PCR检测卵巢HGF、c-Met 的mRNA表达水平。结果 HGF及c-Met蛋白在3、7、14、21 d卵巢中均有表达，且表达量随着小鼠日龄增长而增加（P < 0.05），HGF、c-Met的mRNA水平也呈现相同的趋势（P < 0.05）；生物信息学分析发现HGF /c-Met通路涉及了多种生物学过程及PI3K/AKT等信号通路。结论 HGF/c-Met通路参与小鼠早期卵泡发育，并可能通过细胞内信号通路PI3K/AKT调控原始卵泡启动及卵泡发育的过程。

关键词: 肝细胞生长因子, 肝细胞生长因子受体, 早期卵泡发育

Abstract:

Objective To investigate the role of hepatocyte growth factor and its receptor （c-Met）（HGF/c-Met） signaling pathway in early follicular development in mice via detecting the expression of HGF/c-Met in early mouse ovarian tissue and then analyze the biological process of HGF/c-Met signaling pathway and its possible involvement in intracellular signaling pathways by using bioinformatics for the purpose of further studying the molecular mechanism of the signaling pathway in the early follicle development. Methods Thirty-five female Kunming mice and 15 male ones were fed in 15 cages with the female-to-male ratio of 2∶1. The ovaries of mice at 3， 7， 14 and 21 days after birth were collected. Immunohistochemical staining and Western blotting were applied to detect the expression levels of HGF and c-Met protein in the ovarian tissues. Quantitative Real-time PCR （q-PCR） was used to detect the expression levels of HGF and C-Met mRNA in the early ovarian tissues of mice. Results HGF and c-Met proteins were expressed in the ovarian tissues of the mice at 3， 7， 14 and 21 days， presenting an increasing trend with the increase of age by day （P < 0.05）. The mRNA levels of HGF and c-Met also showed the same trend （P < 0.05）. Bioinformatics analysis revealed that the HGF/c-Met signaling pathway involved in a variety of biological processes and signaling pathways such as PI3K/AKT. Conclusions HGF/c-Met signaling pathway is involved in early follicular development in mice. It may regulate primal follicular initiation and follicular development through intracellular signaling pathway PI3K/AKT.

Key words: HGF, c-Met, early follicular development

中图分类号:

R321.1

黎明星,李卓娴,李康梅,陈秀榕,周艳平,黄愉淋,白琳,吴展帅,夏猛,何国珍. HGF/c-Met信号通路与小鼠早期卵泡发育的相关性研究[J]. 实用医学杂志, 2023, 39(20): 2566-2571.

Mingxing LI,Zhuoxian LI,Kangmei LI,Xiurong CHEN,Yanping ZHOU,Yulin HUANG,Lin BAI,Zhanshuai WU,Meng XIA,Guozhen. HE. Role of hepatocyte growth factor （HGF）/c⁃Met signaling pathway in early follicular development in mice[J]. The Journal of Practical Medicine, 2023, 39(20): 2566-2571.

图/表 6

图1

表1

图2

图3

图4

图5

参考文献 13

1	JOHAM A E， TEEDE H J， RANASINHA S，et al. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome：data from a large community-based cohort study［J］. J Womens Health（Larchmt），2015，24（4）：299-307.
2	CORDTS E B， CHRISTOFOLINI D M， DOS SANTOS A A，et al. Genetic aspects of premature ovarian failure：a literature review［J］. Arch Gynecol Obstet，2011，283（3）：635-643.
3	李康梅，陈秀榕，戴明明，等. HGF/c-Met信号通路调控生殖细胞发生的研究进展［J］. 实用医学杂志，2019，35（21）：3413-3417.
4	GUGLIELMO M C， RICCI G， CATIZONE A，et al. The effect of hepatocyte growth factor on the initial stages of mouse follicle development［J］. J Cell Physiol，2011，226（2）：520-529.
5	RICCI G， CATIZONE A. Pleiotropic Activities of HGF/c-Met System in Testicular Physiology：Paracrine and Endocrine Implications［J］. Front Endocrinol （Lausanne），2014，5：38.
6	ZHANG Y， XIA M， JIN K，et al. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities［J］. Mol Cancer，2018，17（1）：45.
7	GRANITOL A， GUIDETTIL E， GRAMANTIERI L. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma［J］. J Hepatocell Carcinoma，2015，2：29-38.
8	TREMBLAY P G， SIRARD M A. Transcriptomic analysis of gene cascades involved in protein kinase A and C signaling in the KGN line of human ovarian granulosa tumor cells［J］. Biol Reprod，2017，96（4）：855-865.
9	UZUMCU M， PAN Z， CHU Y，et al. Immunolocalization of the hepatocyte growth factor （HGF） system in the rat ovary and the antiapoptotic effect of HGF in rat ovarian granulose cells in vitro［J］. Reproduction，2006，132（2）：291-299.
10	SAHIN N， TOYLU A， GULEKLI B，et al. The levels of hepatocyte growth factor in serum and follicular fluid and the expression of c-Met in granulosa cells in patients with polycystic ovary syndrome［J］. Fertil Steril，2013，99（1）：264-269.
11	欧阳生群，胡波，缪雨青，等. c-Met适配体抑制剂的研究进展［J］. 中国生化药物杂志，2016，36（8）：22-26.
12	李娇娇，焦亚飞，石德顺. PI3K/Akt信号通路对卵泡发育和卵母细胞成熟作用的研究进展［J］. 中国畜牧杂志，2021，57（8）：33-37.
13	戴研平，高晓勤. 慢性砷染毒对大鼠睾丸肝细胞生长因子及其受体c-Met表达的影响［J］. 环境与健康杂志，2017，34（8）：670-673.

日龄	HGF平均光密度	c-Met平均光密度
3 d	0.245 8 ± 0.092 42	0.289 8 ± 0.044 42
7 d	0.333 3 ± 0.003 13^*	0.259 1 ± 0.018 76^*
14 d	0.347 2 ± 0.034 68^*	0.327 8 ± 0.075 23^*
21 d	0.418 2 ± 0.688 90^*	0.330 8 ± 0.069 79^*

HGF/c-Met信号通路与小鼠早期卵泡发育的相关性研究

Role of hepatocyte growth factor （HGF）/c⁃Met signaling pathway in early follicular development in mice

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 13

相关文章 0

编辑推荐

Metrics

本文评价