miR-145靶向Sox9调控PTHrP及其下游信号通路在鹿茸间充质干细胞成软骨分化中的作用机制研究
结题报告
批准号:
32002171
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
贾博寅
依托单位:
学科分类:
家禽及其他经济动物种质资源与遗传育种学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
贾博寅
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中文摘要
鹿茸间充质干细胞(MSCs)可高度增殖并不断向软骨分化,维持鹿茸快速生长却不发生癌变,但其调控鹿茸快速生长的分子机制尚不清楚。项目组前期对不同生长期鹿茸全转录组测序发现,miR-145、Sox9、PTHrP之间存在表达量相关性,双荧光素酶实验证实miR-145能通过Sox9基因的3'UTR区的特定位点对其进行调节。已有报道miR-145靶向抑制Sox9,且Sox9促进PTHrP表达,而PTHrP是鹿茸MSCs成软骨分化的重要调控基因。故提出假设:鹿茸MSCs成软骨分化过程中,miR-145通过靶向Sox9调控PTHrP及其下游信号通路抑制鹿茸MSCs成软骨分化。本项目拟采用分子生物学技术研究miR-145、Sox9、PTHrP在鹿茸MSCs成软骨分化中的作用及调控路径,揭示miR-145调控鹿茸MSCs成软骨分化的分子机制,为鹿茸快速生长机理及以鹿茸为模型开展软骨组织缺损修复提供科学依据。
英文摘要
Antler mesenchymal stem cells (MSCs) can highly proliferate and constantly differentiate into the cartilage, which maintains the rapid growth of antler without carcinogenesis. However, the molecular mechanism of MSCs regulating the rapid growth of antler is unclear. The whole transcriptome sequencing of antler in different growth stages were performed by the applicant in the previous experiments. The results showed that there was a correlation between the expression levels of miR-145, Sox9, and PTHrP. Besides, dual-luciferase reporter assay system showed that miR-145 could regulate 3'UTR region of Sox9 gene. It has been reported that miR-145 inhibited Sox9, and Sox9 promoted the expression of PTHrP, which was an important regulatory gene in chondrogenic differentiation of antler MSCs. Therefore, we propose the hypothesis that miR-145 inhibits the cartilage differentiation of antler MSCs by targeting Sox9 to regulate PTHrP and its downstream signaling pathways. This project aims to study the role and regulatory pathways of miR-145, Sox9, PTHrP in chondrogenic differentiation of antler MSCs by using molecular biology techniques, then reveal further the regulation mechanism of miR-145 in chondrogenic differentiation of antler MSCs. The obtained results provide a scientific basis for the rapid growth mechanism of antler and the repair of cartilage defect using antler as the model.
期刊论文列表
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专利列表
DOI:10.1007/s00438-021-01776-z
发表时间:2021-03-26
期刊:MOLECULAR GENETICS AND GENOMICS
影响因子:3.1
作者:Jia, Boyin;Zhang, Linlin;Ba, Hengxing
通讯作者:Ba, Hengxing
DOI:10.1002/aro2.18
发表时间:2023-08
期刊:Animal Research and One Health
影响因子:--
作者:Boyin Jia;Xin Li;Xintong Han;Fuquan Ma;Linlin Zhang;Xue Wang;Xinrui Yan;Yu Zhang;Jian-ming Li;P. Hu;Yusu Wang;Naichao Diao;Kun Shi;Ying Zong;Rui Du;Chunyi Li
通讯作者:Boyin Jia;Xin Li;Xintong Han;Fuquan Ma;Linlin Zhang;Xue Wang;Xinrui Yan;Yu Zhang;Jian-ming Li;P. Hu;Yusu Wang;Naichao Diao;Kun Shi;Ying Zong;Rui Du;Chunyi Li
DOI:10.3389/fvets.2022.854503
发表时间:2022
期刊:Frontiers in veterinary science
影响因子:3.2
作者:
通讯作者:
DOI:10.3389/fvets.2022.1042445
发表时间:2022
期刊:FRONTIERS IN VETERINARY SCIENCE
影响因子:3.2
作者:Jia, Boyin;Wang, Xue;Ma, Fuquan;Li, Xin;Han, Xintong;Zhang, Linlin;Li, Jianming;Diao, Naichao;Shi, Kun;Ge, Chenxia;Yang, Fuhe;Du, Rui
通讯作者:Du, Rui
国内基金
海外基金