Dysfunctional resident lung mesenchymal stem cells contribute to pulmonary microvascular remodeling.
Dysfunctional resident lung mesenchymal stem cells contribute to pulmonary microvascular remodeling.
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DOI：
10.4103/2045-8932.109912
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发表时间：
2013-01
影响因子：
2.6
通讯作者：
Majka SM
中科院分区：
文献类型：
--
作者：
Chow K;Fessel JP;Kaoriihida-Stansbury;Schmidt EP;Gaskill C;Alvarez D;Graham B;Harrison DG;Wagner DH Jr;Nozik-Grayck E;West JD;Klemm DJ;Majka SM
肺血管重构和氧化应激是许多成人肺部疾病的共同特点。然而，很少有人知道肺间充质干细胞（MSC）在这些过程中的相关性。我们检验了功能障碍的肺间充质干细胞直接参与微循环重塑的假设。我们采用了一个遗传模型，耗尽细胞外超氧化物歧化酶（EC-SOD）在肺间充质干细胞加上谱系追踪分析。我们将ABCG 2启动子控制下的Cre重组酶表达菌株与pepsod 3和mT/mG报告小鼠杂交。我们证明在体内，耗尽EC-SOD在肺间充质干细胞的平滑肌肌动蛋白阳性层的微血管重塑的贡献。我们进一步将肺间充质干细胞鉴定为多能血管前体，能够在体外分化为肌成纤维细胞、内皮细胞和周细胞。EC-SOD缺乏可促进肺间充质干细胞的增殖和凋亡，限制其集落形成能力和多向分化潜能，并促进其向收缩表型的转变。进一步的研究将细胞功能障碍与经典Wnt/β-连环蛋白信号传导的改变相关联，这在氧化应激条件下更明显。我们的数据证实，肺MSC是多能血管前体群体，其具有参与血管重塑的能力，并且其功能可能部分由Wnt/β-连环蛋白信号传导途径调节。这些研究强调了微环境调节多能MSC功能的重要作用以及它们促进组织重塑的潜力。
Pulmonary vascular remodeling and oxidative stress are common to many adult lung diseases. However, little is known about the relevance of lung mesenchymal stem cells (MSCs) in these processes. We tested the hypothesis that dysfunctional lung MSCs directly participate in remodeling of the microcirculation. We employed a genetic model to deplete extracellular superoxide dismutase (EC-SOD) in lung MSCs coupled with lineage tracing analysis. We crossed floxpsod3 and mT/mG reporter mice to a strain expressing Cre recombinase under the control of the ABCG2 promoter. We demonstrated In vivo that depletion of EC-SOD in lung MSCs resulted in their contribution to microvascular remodeling in the smooth muscle actin positive layer. We further characterized lung MSCs to be multipotent vascular precursors, capable of myofibroblast, endothelial and pericyte differentiation in vitro. EC-SOD deficiency in cultured lung MSCs accelerated proliferation and apoptosis, restricted colony-forming ability, multilineage differentiation potential and promoted the transition to a contractile phenotype. Further studies correlated cell dysfunction to alterations in canonical Wnt/β-catenin signaling, which were more evident under conditions of oxidative stress. Our data establish that lung MSCs are a multipotent vascular precursor population, a population which has the capacity to participate in vascular remodeling and their function is likely regulated in part by the Wnt/β-catenin signaling pathway. These studies highlight an important role for microenviromental regulation of multipotent MSC function as well as their potential to contribute to tissue remodeling.
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影响因子：
2.7
作者：
De langhe, Stijn P.;Carraro, Gianni;Bellusci, Saverio
通讯作者：
Bellusci, Saverio
DOI：
10.1164/rccm.200902-0242oc
发表时间：
2009-12-01
影响因子：
24.7
作者：
Aslam, Muhammad;Baveja, Rajiv;Kourembanas, Stella
通讯作者：
Kourembanas, Stella
DOI：
10.1152/ajplung.00149.2003
发表时间：
2004-04-01
影响因子：
4.9
作者：
Giangreco, A;Shen, HM;Stripp, BR
通讯作者：
Stripp, BR
影响因子：
4
作者：
Baksh, Dolores;Boland, Genevieve M.;Tuan, Rocky S.
通讯作者：
Tuan, Rocky S.
影响因子：
15.9
作者：
Beers, Michael F.;Morrisey, Edward E.
通讯作者：
Morrisey, Edward E.