Transplantation of bone marrow cells from miR150 knockout mice improves senescence-associated humoral immune dysfunction and arterial stiffness.
Transplantation of bone marrow cells from miR150 knockout mice improves senescence-associated humoral immune dysfunction and arterial stiffness.
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DOI：
10.1016/j.metabol.2022.155249
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发表时间：
2022-09
期刊：
影响因子：
--
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Fan J;Wang S;Lu X;Sun Z
衰老加速小鼠P1（SAMP 1）患有体液免疫缺陷、动脉硬化和加速衰老。相比之下，microRNA-150敲除（miR-150-KO）小鼠显示增强的体液免疫功能，包括增加的B细胞群体和升高的血清免疫球蛋白水平，并享有延长的寿命。本研究的目的是研究移植来自miR-150-KO小鼠的骨髓细胞（BMC）是否影响SAMP 1小鼠的免疫缺陷和动脉硬化。SAMP 1小鼠（10个月）的脉搏波速度和血压显著增加，表明动脉硬化和高血压。有趣的是，移植来自miR-150-KO小鼠的BMC在8周内显著减轻了SAMP 1小鼠的动脉硬化和高血压。来自miR-150-KO小鼠的BMC移植部分挽救了B淋巴细胞的下调，大大恢复了血清IgG和IgM水平，降低了炎症细胞因子和趋化因子的表达，并减弱了SAMP 1小鼠主动脉中巨噬细胞和T细胞的浸润。BMC移植几乎消除了SAMP 1小鼠滑膜中胶原1、TGFβ1、巩膜轴、MMP-2和MMP-9表达的上调以及弹性蛋白水平的下调。实验结束时，FISH染色证实移植的BMCs的存在。在培养的内皮细胞中，IgG缺陷培养基引起炎性细胞因子/趋化因子表达的上调，这可以通过用IgG处理来挽救。加速衰老通过损害SAMP 1小鼠的体液免疫功能引起动脉硬化。miR-150-KO小鼠的BMC移植部分通过改善体液免疫功能减轻血管炎症，从而减轻SAMP 1小鼠的动脉基质重塑和硬化以及高血压。
The senescence-accelerated mouse P1 (SAMP1) suffers from humoral immune deficiency, arterial stiffness and accelerated aging. In contrast, the microRNA-150 knockout (miR-150-KO) mice show enhanced humoral immune function including increased B cell population and elevated serum immunoglobulin levels and enjoy extended lifespan. The purpose of this study was to investigate whether transplantation of bone marrow cells (BMCs) from miR-150-KO mice affects immune deficiency and arterial stiffening in SAMP1 mice. Pulse wave velocity and blood pressure were increased significantly in SAMP1 mice (10 months), indicating arterial stiffening and hypertension. Interestingly, transplantation of BMCs from miR-150-KO mice significantly attenuated arterial stiffening and hypertension in SAMP1 mice within eight weeks. BMC transplantation from miR-150-KO mice partially rescued the downregulation of B lymphocytes, largely restored serum IgG and IgM levels, decreased inflammatory cytokine and chemokine expression, and attenuated macrophage and T cell infiltration in aortas in SAMP1 mice. BMC transplantation nearly abolished the upregulation of collagen 1, TGFβ1, Scleraxis, MMP-2 and MMP-9 expression and the downregulation of elastin levels in aortas in SAMP1 mice. FISH staining confirmed existence of the transplanted BMCs at end of the experiment. In cultured endothelial cells, IgG-deficient medium invoked upregulation of inflammatory cytokine/chemokine expression which can be rescued by treatment with IgG. Accelerated senescence caused arterial stiffening via impairing the humoral immune function in SAMP1 mice. BMC transplantation from miR-150-KO mice attenuated arterial matrix remodeling and stiffening and hypertension in SAMP1 mice partly via improving the humoral immune function which attenuates vascular inflammation.
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影响因子：
20.1
作者：
Chen K;Wang S;Sun QW;Zhang B;Ullah M;Sun Z
通讯作者：
Sun Z
影响因子：
16
作者：
Feng, Rui;Ullah, Mujib;Sun, Zhongjie
通讯作者：
Sun, Zhongjie
DOI：
10.1161/hypertensionaha.116.07709
发表时间：
2016-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Gao D;Zuo Z;Tian J;Ali Q;Lin Y;Lei H;Sun Z
通讯作者：
Sun Z
影响因子：
5.6
作者：
Koh YC;Yang G;Lai CS;Weerawatanakorn M;Pan MH
通讯作者：
Pan MH
影响因子：
8.3
作者：
Chan, Christopher T.;Sobey, Christopher G.;Drummond, Grant R.
通讯作者：
Drummond, Grant R.