ANRIL竞争性结合microRNA-143调控L型钙离子通道对血管重构的作用及机制

The main mechanism of vascular remodeling is the phenotypic switching of vascular smooth muscle cells (VSMCs). The phenotypic switching of VSMCs is inhibited when the expression of CACNA1C coding the α1-subunit of L-type calcium channel (LTCC) is increased and the function of LTCC is enhanced, and microRNA-143 (miR-143) combining CACNA1C mRNA may up-regulates the expression of CACNA1C and the function of LTCC. It's possible that long noncoding RNA (lncRNA) ANRIL may stimulates the phenotypic switching of VSMCs. Proposer has noticed that ANRIL is involved in the regulation of vascular remodeling in preliminary experiment, and found the predicted combining sites of miR-143 in ANRIL sequences. So proposer presumes that ANRIL combines miR-143 competing with CACNA1C mRNA, and inhibits the expression of CACNA1C and the function of LTCC, thus stimulates the phenotypic switching of VSMCs and vascular remodeling. This study will establish mice models and cell models, verify that ANRIL acts on vascular remodeling through competitively combining miR-143 to regulate LTCC by electrophoretic mobility shift assay and developing luciferase reporter vector. This study discusses the relationship between lncRNA and LTCC for the first time which has clear innovativeness and academic value.

血管重构的主要机制是血管平滑肌细胞表型转化。编码L型钙离子通道(LTCC) α1亚基的CACNA1C表达增加和LTCC功能增强会抑制表型转化。而microRNA-143(miR-143)与CACNA1C mRNA结合可增加CACNA1C表达和增强LTCC功能。长链非编码RNA(lncRNA) ANRIL可促进表型转化。申请人在预实验中发现ANRIL参与调节血管重构，且在ANRIL序列上找到miR-143预测结合位点。故推测ANRIL通过与CACNA1C mRNA竞争性结合miR-143，抑制CACNA1C表达和减弱LTCC功能，促进表型转化和血管重构。本项目将建立小鼠和细胞模型，通过电泳迁移率实验和构建荧光素酶报告基因载体，验证ANRIL竞争性结合miR-143调控LTCC以作用于血管重构。本项目首次探索lncRNA与LTCC之间关系，具有明确的创新性和学术价值。

血管重构的主要机制是血管平滑肌细胞表型转化。编码L型钙离子通道(LTCC) α1亚基的CACNA1C表达增加和LTCC功能增强会抑制表型转化。而microRNA-143(miR-143)与CACNA1C mRNA结合可增加CACNA1C表达和增强LTCC功能。长链非编码RNA(lncRNA) ANRIL可促进表型转化。申请人在预实验中发现ANRIL参与调节血管重构，且在ANRIL序列上找到miR-143预测结合位点。故推测ANRIL通过与CACNA1C mRNA竞争性结合miR-143，抑制CACNA1C表达和减弱LTCC功能，促进表型转化和血管重构。本项目将建立小鼠和细胞模型，通过电泳迁移率实验和构建荧光素酶报告基因载体，验证ANRIL竞争性结合miR-143调控LTCC以作用于血管重构。本项目首次探索lncRNA与LTCC之间关系，具有明确的创新性和学术价值。