激活素A调控JAK2V617F突变干细胞分化异常促进心肌纤维化的作用机制研究

批准号:
81970209
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
杨萍
依托单位:
学科分类:
心肌损伤、修复、重构和再生
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
杨萍
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中文摘要
骨髓增殖性肿瘤(MPN)易伴发心脏损伤,其机制不明。我们既往研究发现JAK2V617F突变的MPN小鼠心肌纤维化增加。JAK2V617F突变主要引起JAK通路持续激活、骨髓干细胞分化异常,而激活JAK通路可增加细胞增殖和分化关键调控因子激活素A(Activin A)的分泌。我们前期实验已观察到激活素A促进心肌纤维化。因此推测,激活素A参与JAK2V617F突变MPN骨髓干细胞向心肌成纤维细胞异常分化的调控。本项目将通过转基因动物模型、干细胞示踪等方法,明确激活素A在 JAK2V617F突变MPN骨髓干细胞分化为成纤维细胞中的调控作用;利用蛋白芯片技术寻找关键的调控分子,并结合CRISPR/Cas9基因编辑等方法干预相关分子的表达,阐明激活素A调控JAK2V617F突变MPN骨髓干细胞异常分化促进心肌纤维化的分子机制,为肿瘤心脏病的研究和有效干预提供新的视野。
英文摘要
Myeloproliferative neoplasms (MPN) are prone to cardiac injury, and the underlying mechanism is unclear. Our previous studies found that myocardial fibrosis increased in MPN mice with JAK2V617F mutation. JAK2V617F mutation leads to consistent activation of JAK signaling pathway andabnormal differentiation of bone marrow stem cells. Activation of JAK pathway can increase the secretion of Activin A, a key regulator of cell proliferation and differentiation. We have observed that activin A leads to myocardial fibrosis in our previous experiments. Therefore, we speculate that activin A is involved in the regulation of abnormal differentiation of bone marrow stem cells from MPN with JAK2V617F mutant into cardiac fibroblasts. In this study, we will clarify the regulatory mechanism of activin A in the differentiation of bone marrow stem cells from MPN with JAK2V617F mutant into fibroblasts through experimental techniques such as transgenic animal models and stem cell tracing. We will also use protein chip technology to find key regulators, and combine CRISPR/Cas9 gene editing and other methods to interfere with the expression of related molecules. This project will elucidate the molecular mechanism of activin A regulating abnormal differentiation of bone marrow stem cells from MPN with JAK2V617F mutant to promote myocardial fibrosis, and provide a new perspective for the research and effective intervention of cancer heart disease.
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DOI:10.1136/bmjopen-2022-071473
发表时间:2023-06-19
期刊:BMJ OPEN
影响因子:2.9
作者:Tian, Zhuang;Wang, Fang;Jin, Wei;Zhang, Qing;Zhou, Jingmin;Yang, Ping;Wang, Geng;Hsu, Peiwen;Sun, Jing;Zhang, Shuyang;Han, Yaling
通讯作者:Han, Yaling
Transcriptomic Bioinformatic Analyses of Atria Uncover Involvement of Pathways Related to Strain and Post-translational Modification of Collagen in Increased Atrial Fibrillation Vulnerability in Intensely Exercised Mice.
心房的转录组生物信息学分析揭示了与胶原蛋白应变和翻译后修饰相关的通路在剧烈运动小鼠心房颤动脆弱性增加中的参与。
DOI:10.3389/fphys.2020.605671
发表时间:2020
期刊:Frontiers in physiology
影响因子:4
作者:Oh Y;Yang S;Liu X;Jana S;Izaddoustdar F;Gao X;Debi R;Kim DK;Kim KH;Yang P;Kassiri Z;Lakin R;Backx PH
通讯作者:Backx PH
DOI:10.7150/ijms.70614
发表时间:2022
期刊:INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
影响因子:3.6
作者:Li, Xiangdong;Wang, Zhiyuan;Meng, Heyu;Meng, Fanbo;Yang, Ping
通讯作者:Yang, Ping
A new peripheral endothelial function measurement improves prediction of symptomatic coronary artery disease
一种新的外周内皮功能测量方法可改善症状性冠状动脉疾病的预测
DOI:10.1177/0300060520932818
发表时间:2020
期刊:The Journal of International Medical Research
影响因子:--
作者:B. Du;D. Si;Dong Zhao;Yanan Zhao;K. Wagatsuma;Yuquan He;Ping Yang
通讯作者:Ping Yang
DOI:10.3389/fcvm.2021.758035
发表时间:2021
期刊:Frontiers in cardiovascular medicine
影响因子:3.6
作者:Meng H;Ruan J;Chen Y;Yan Z;Shi K;Li X;Yang P;Meng F
通讯作者:Meng F
Ghrelin通过miR-208家族调控UCP2表达改善心衰心肌代谢重构的机制研究
- 批准号:81570360
- 项目类别:面上项目
- 资助金额:52.0万元
- 批准年份:2015
- 负责人:杨萍
- 依托单位:
激活素A/卵泡抑素系统失衡在心衰心肌细胞凋亡中的作用及机制
- 批准号:81270315
- 项目类别:面上项目
- 资助金额:55.0万元
- 批准年份:2012
- 负责人:杨萍
- 依托单位:
生长激素对于心衰心肌细胞凋亡抑制及内皮细胞保护作用的研究
- 批准号:30770883
- 项目类别:面上项目
- 资助金额:30.0万元
- 批准年份:2007
- 负责人:杨萍
- 依托单位:
国内基金
海外基金
