中国药理学通报2024，Vol.40Issue(1)：55-62,8.DOI:10.12360/CPB202304049
LncRNA p21调控Hippo-YAP信号通路对小鼠腹主动脉瘤形成的影响及机制
Effect of LncRNA p21 regulating Hippo-YAP signaling pathway on formation of abdominal aortic aneurysm in mice and its mechanism
摘要
Abstract
Aim To investigate the effect of long non-coding RNA p21(LncRNA p21)regulating Hippo-Yes-associated protein(Hippo-YAP)signaling path-way on the formation of abdominal aortic aneurysm(AAA)in mice.Methods C57BL/6 ApoE-/-mouse model of AAA induced by angiotensin Ⅱ(AngⅡ)was established by subcutaneously implanting os-motic micropumps.C57BL/6 ApoE-/-mice were ran-domly divided into sham operation group(sham),model group(model),LncRNA p21 negative control group(sh-NC),LncRNA p21 knockdown group(sh-LncRNAp21).Hematoxylin-staining(HE)and Ver-hoeff-Van Gieson(VVG)were used to observe the morphological changes of blood vessels.qRT-PCR was used to detect the expression of LncRNA p21.Western blot was used to detect the expression of MMP-2,MMP-9 and TIMP-1.TUNEL staining was used to de-tect the apoptosis of smooth muscle cells.Western blot was used to detect the expression of caspase-3,cy-clinD1 and Hippo-YAP signaling pathway proteins.Results Compared with the sham group,the vascular elastic fibers were disrupted and damaged,the expres-sions of LncRNA p21,MMP-2,MMP-9,caspase-3 and rate of apoptosis all increased(P＜0.01),and the expressions of TIMP-1,cyclinD1 and YAP,TAZ decreased in the model group(P＜0.01).Compared with the model group,the vascular elastic fibers were less broken and damaged,and the expressions of Ln-cRNA p21,MMP-2,MMP-9,caspase-3 and the rate of apoptosis all decreased(P＜0.01),both TIMP-1,cyclinD1 and YAP,TAZ expressions were raised in the sh-LncRNA p21 group(P＜0.01).Conclusions LncRNA p21 can promote the formation of AAA in mice,and its mechanism is related to regulating Hip-po-YAP signal,promoting cell apoptosis and inhibiting cell proliferation.关键词
腹主动脉瘤/长链非编码RNA p21/Hippo-Yes相关蛋白通路/凋亡/增殖/小鼠Key words
abdominal aortic aneurysm/long non-cod-ing RNA p21/Hippo-Yes-related protein pathway/ap-optosis/proliferation/mice分类
医药卫生引用本文复制引用
陈啸,王晋军,张林林,郭莲莲,张中旺,张娟子..LncRNA p21调控Hippo-YAP信号通路对小鼠腹主动脉瘤形成的影响及机制[J].中国药理学通报,2024,40(1):55-62,8.基金项目
国家自然科学基金资助项目(No 82172095) （No 82172095）
山东省医药卫生科技发展计划项目(No 202104130109) （No 202104130109）
