Putative endothelial progenitor cells do not promote vascular repair but attenuate pericyte-myofibroblast transition in UUO-induced renal fibrosis
Putative endothelial progenitor cells do not promote vascular repair but attenuate pericyte-myofibroblast transition in UUO-induced renal fibrosis
复制标题
在 UUO 诱导的肾纤维化中，假定的内皮祖细胞不会促进血管修复，但会减弱周细胞-肌成纤维细胞的转变
DOI：
10.1186/s13287-019-1201-5
复制
发表时间：
2019-03-21
影响因子：
7.5
通讯作者：
Yao, Ying
中科院分区：
文献类型：
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作者：
Yang, Juan;Wang, Meng;Yao, Ying
背景：内皮祖细胞（pEPCs）已被证实参与缓解几种缺血性疾病的肾纤维化。然而，它们对肾纤维化的机制作用，其特征是血管退化和进一步的稀疏相关病理，仍不清楚。方法：从小鼠骨髓中分离pEPCs，探讨pEPCs在单侧输尿管梗阻（UUO）所致肾纤维化中的作用及其分子机制。在体内，通过尾静脉向UUO小鼠注射pepc （2 × 10(5)个细胞/天）和pepc - mv（微泡）。体外，pEPCs与肾源性周细胞共培养。使用肌成纤维细胞标记α -平滑肌肌动蛋白（α - sma）和周细胞标记血小板衍生生长因子受体β (pdgfr - β)评估周细胞-肌成纤维细胞转化。结果：在UUO模型中，外源性骨髓来源的pEPCs通过减少周细胞-肌成纤维细胞的转变来减轻肾纤维化，但没有明显的血管修复。结果表明，pepc通过pepc - mv调控周细胞向肌成纤维细胞的转变。周细胞与pEPCs体外共培养表明，pEPCs通过旁分泌途径抑制转化生长因子- β (tgf - β)诱导的周细胞向肌成纤维细胞转变。结论：EPCs通过旁分泌途径抑制周细胞-肌成纤维细胞转化，有效减轻uuo诱导的肾纤维化，但不促进血管修复。
Background: Putative endothelial progenitor cells (pEPCs) have been confirmed to participate in alleviation of renal fibrosis in several ischaemic diseases. However, their mechanistic effect on renal fibrosis, which is characterized by vascular regression and further rarefaction-related pathology, remains unknown.Methods: To explore the effect and molecular mechanisms by which pEPCs act on unilateral ureteral obstruction (UUO)-induced renal fibrosis, we isolated pEPCs from murine bone marrow. In vivo, pEPCs (2x10(5) cells/day) and pEPC-MVs (microvesicles) were injected into UUO mice via the tail vein. In vitro, pEPCs were co-cultured with renal-derived pericytes. Pericyte-myofibroblast transition was evaluated using the myofibroblast marker alpha-smooth muscle actin (alpha-SMA) and pericyte marker platelet-derived growth factor receptor beta (PDGFR-beta).Results: Exogenous supply of bone marrow-derived pEPCs attenuated renal fibrosis by decreasing pericyte-myofibroblast transition without significant vascular repair in the UUO model. Our results indicated that pEPCs regulated pericytes and their transition into myofibroblasts via pEPC-MVs. Co-culture of pericytes with pEPCs in vitro suggested that pEPCs inhibit transforming growth factor-beta (TGF-beta)-induced pericyte-myofibroblast transition via a paracrine pathway.Conclusionp: EPCs effectively attenuated UUO-induced renal fibrosis by inhibiting pericyte-myofibroblast transition via a paracrine pathway, without promoting vascular repair.