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./nMethods: 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./nResults: 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./nConclusion: Exogenous b-pEPCs directly protect against IR-induced vascular injury and prevent renal fibrosis by inhibiting the activation of PDGFR-β-positive pericytes.

中文翻译：

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外源性骨髓来源的内皮祖细胞减轻依赖于周细胞的小鼠缺血再灌注引起的血管损伤和肾纤维化

原理：毛细血管由内皮细胞和周围的壁细胞，周细胞组成。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作用。外源性骨髓来源的内皮祖细胞（b-pEPCs）具有修复血管的潜力。然而，它们对受损肾脏中的血管结构稳定和与周细胞相关的病理生物学结果的影响尚未得到全面检查。我们应用缺血再灌注（IR）诱导小鼠的肾血管损伤和肾纤维化。产生了血小板衍生的生长因子受体β（PDGFR-β）-DTR阳性小鼠，以耗尽周细胞，并使用外源性b-pEPC和PDGFR-β配体PDGF链B（PDGF-BB）来探索这种关系。在b-pEPC，周细胞，血管修复和早期肾纤维化中。b-pEPCs的给药通过旁分泌模式减少了IR诱导的周细胞-内皮脱离，周细胞增殖和成纤维细胞转化，不仅保留了血管稳定，而且改善了IR引发的肾纤维化。PDGF-BB上调了PDGFR-β的表达，加剧了血管异常，并通过b-pEPCs的给药改善了周细胞-成肌纤维细胞的转化。外源性b-pEPCs及其培养基（CM）诱导的血管损伤保护作用，并通过选择性清除周细胞来阻断肾纤维化。/n结论：外源性b-pEPCs可直接抑制IR诱导的血管损伤并通过抑制作用来预防肾纤维化PDGFR-β阳性周细胞的活化。