Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes.
Exogenous bone marrow derived-putative endothelial progenitor cells attenuate ischemia reperfusion-induced vascular injury and renal fibrosis in mice dependent on pericytes.
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外源性骨髓来源的假定内皮祖细胞减轻依赖于周细胞的小鼠缺血再灌注诱导的血管损伤和肾纤维化
作者：
Wang M;Xu H;Li Y;Cao C;Zhu H;Wang Y;Zhao Z;Pei G;Zhu F;Yang Q;Deng X;Zhou C;Guo Y;Wu J;Liao W;Yang J;Yao Y;Zeng R
基本原理：毛细血管是由内皮细胞和周围的壁细胞，周细胞。损伤后的微血管修复不仅涉及内皮细胞的增殖，还涉及基于周细胞的血管稳定。外源性骨髓来源的推定内皮祖细胞（b-pEPCs）具有血管修复的潜力，然而，其对血管结构的稳定性和周细胞相关的病理生物学结果在损伤的肾脏尚未得到充分的研究。方法：采用肾缺血再灌注（IR）方法，造成小鼠肾血管损伤和肾纤维化。产生血小板衍生生长因子受体β（PDGFR-β）-DTR阳性小鼠以消耗周细胞，并使用外源性b-pEPCs和PDGFR-β配体PDGF链B（PDGF-BB）来探索b-pEPCs、周细胞、血管修复和早期肾纤维化之间的关系。结果如下：b-pEPCs通过旁分泌模式减少了IR诱导的周细胞-内皮细胞脱离、周细胞增殖和肌成纤维细胞转变，这不仅保持了血管稳定，而且改善了IR引发的肾纤维化。PDGF-BB上调PDGFR-β的表达，加重血管异常和周细胞-肌成纤维细胞转化，这些都被b-pEPCs给药所改善。外源性b-pEPCs及其培养液（CM）诱导血管损伤保护，并通过选择性去除周细胞来阻断肾纤维化。结论：外源性b-pEPCs通过抑制PDGFR-β阳性周细胞的活化直接保护IR诱导的血管损伤并预防肾纤维化。
Rationale: Capillaries are composed of endothelial cells and the surrounding mural cells, pericytes. Microvascular repair after injury involves not only the proliferation of endothelial cells but also pericyte-based vessel stabilization. Exogenous bone marrow derived-putative endothelial progenitor cells (b-pEPCs) have the potential for vascular repair; however, their effect on vascular structure stabilization and pericyte-related pathobiological outcomes in the injured kidney has not been fully examined. Methods: We applied ischemia-reperfusion (IR) to induce renal vascular injury and renal fibrosis in mice. Platelet-derived growth factor receptor β (PDGFR-β)-DTR-positive mice were generated to deplete pericytes, and exogenous b-pEPCs and the PDGFR-β ligand, PDGF chain B (PDGF-BB), were employed to explore the relationship among b-pEPCs, pericytes, vascular repair, and early renal fibrosis. Results: Administration of b-pEPCs reduced IR-induced pericyte-endothelial detachment, pericyte proliferation, and myofibroblast transition via a paracrine mode, which preserved not only vascular stabilization but also ameliorated IR-initiated renal fibrosis. PDGF-BB upregulated the expression of PDGFR-β, exacerbated vascular abnormality, and pericyte-myofibroblast transition, which were ameliorated by b-pEPCs administration. The exogenous b-pEPCs and their culture medium (CM) induced vascular injury protection, and renal fibrosis was blocked by selective deletion of pericytes. Conclusion: Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.
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DOI：
10.1016/j.omtn.2018.09.005
发表时间：
2018-12-07
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Steinle H;Golombek S;Behring A;Schlensak C;Wendel HP;Avci-Adali M
通讯作者：
Avci-Adali M
影响因子：
13.6
作者：
Schrimpf, Claudia;Xin, Cuiyan;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
DOI：
10.1073/pnas.1814874116
发表时间：
2019-04-09
影响因子：
11.1
作者：
Liu, Chang;Ge, Hui-Min;Yan, Biao
通讯作者：
Yan, Biao
LncRNA WTAPP1 通过 MicroRNA 3120 和 Akt/PI3K/自噬途径通过 MMP1 促进内皮祖细胞的迁移和血管生成
影响因子：
5.2
作者：
Li, Wen-Dong;Zhou, Dong-Ming;Li, Xiao-Qiang
通讯作者：
Li, Xiao-Qiang
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC