母猪外周脂肪来源的外泌体内脂素调控胎盘血管生成的机制

批准号:
32002187
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
周远飞
依托单位:
学科分类:
动物营养学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
周远飞
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中文摘要
母猪妊娠期良好胎盘血管网络是保障胎儿健康发育的关键。过肥母猪胎盘血管受损、弱仔率高,但过多体脂如何对胎盘血管生成的远程调控尚不清楚。最近报道,脂肪来源外泌体是细胞间交流的新方式,我们发现母猪脂肪来源的外泌体内脂素可能是影响血管内皮细胞功能的重要因子。我们假设:母猪妊娠过肥,脂肪来源的外泌体内脂素降低,进入胎盘血管内皮细胞后释放减少,抑制了血管生成。拟构建脂肪肥大细胞模型及外泌体释放抑制剂处理肥大细胞,证实内脂素是负载脂质的脂肪细胞外泌体分泌的;在脂肪肥大细胞和血管内皮细胞共培养中,研究内脂素对血管生成的影响;用内脂素重组蛋白处理胎盘血管内皮细胞,检测NAD+、SIRT1水平和活性,联合RNA-seq测序、启动子荧光素酶报告系统和ChIP技术靶定受内脂素-NAD+-SIRT1调控的关键基因,并验证其功能及胎盘富集水平。项目为揭示母猪体况影响胎盘血管发育提供新思路,对实现背膘管理提供理论依据。
英文摘要
The optimal placental vascular network is an important role in the development of healthy fetus during pregnancy. Our previous study indicated that excess backfat of sows during gestation is associated with more serious disturbance of development of placental vasculature and increasing proportion of intrauterine growth restriction piglets. However, how excessive body fat during gestation of sows can achieve remote and regulate placental angiogenesis is still unclear. Recently, it was demonstrated that adipose tissue is a major source of circulating exosomes. We found that adipocyte-derived exosomes visfatin from the sows may be a new important factor affecting the function of vascular endothelial cells. The hypothesis is that the excess backfat of sows during gestation inhibits the secretion of adipocyte-derived exosomal visfatin, is transmitted and released in the placenta reducing, resulting in angiogenesis disorder. The content of this study is as follow, to construct an in vitro model of adipose mast cells or treat mast cells with exosome release inhibitors, to confirm lipid-loaded adipocyte-derived visfatin is secreted in exosomes. Using model of co-culture of adipose mast cells and vascular endothelial cells, to study the effect of visfatin on angiogenesis. To treat the placental vascular endothelial cells with visfatin recombinant protein, the levels and activing of NAD+, SIRT1 will be detected. And using RNA-seq and promoter luciferase reporting system and ChIP assay to screen and identify the key target gene of visfatin-NAD+-SIRT1 signaling pathways. The function of angiogenesis of the key target gene will be verified. Furthermore, the distribution and enrichment of key target genes in placental tissues of sows with different body conditions will be detected, and to establish the relationship between sows body conditions, target genes and angiogenesis of placental tissues. This study provides a new idea to elucidate the influence of sow body condition on the angiogenesis of placenta, and provides theoretical basis for backfat management of the sow production.
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DOI:10.13376/j.cbls/2023071
发表时间:2023
期刊:生命科学
影响因子:--
作者:段兵兵;王方珂;周远飞
通讯作者:周远飞
DOI:10.3390/nu14112230
发表时间:2022-05-26
期刊:Nutrients
影响因子:5.9
作者:
通讯作者:
DOI:10.3390/ijms221910343
发表时间:2021-09-26
期刊:International journal of molecular sciences
影响因子:5.6
作者:Zhou Y;Xia M;Cui C;Wei H;Jiang S;Peng J
通讯作者:Peng J
亚精胺通过eIF5A-羟腐胺赖氨酸修饰影响母猪胎盘血管生成的机制
- 批准号:32372906
- 项目类别:面上项目
- 资助金额:50万元
- 批准年份:2023
- 负责人:周远飞
- 依托单位:
国内基金
海外基金
