Tubular cell-derived exosomal miR-150-5p contributes to renal fibrosis following unilateral ischemia-reperfusion injury by activating fibroblast in vitro and in vivo.
Tubular cell-derived exosomal miR-150-5p contributes to renal fibrosis following unilateral ischemia-reperfusion injury by activating fibroblast in vitro and in vivo.
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肾小管细胞来源的外泌体 miR-150-5p 通过激活体外和体内成纤维细胞，促进单侧缺血再灌注损伤后的肾纤维化
DOI：
10.7150/ijbs.62478
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发表时间：
2021
影响因子：
9.2
通讯作者：
Cheng F
中科院分区：
文献类型：
--
作者：
Zhou X;Zhao S;Li W;Ruan Y;Yuan R;Ning J;Jiang K;Xie J;Yao X;Li H;Li C;Rao T;Yu W;Cheng F
缺血时间较长的单侧缺血再灌注损伤（UIRI）与急性肾损伤和慢性肾脏疾病的风险增加有关。外泌体可以将脂质、蛋白质、mRNA和miRNA转运到相应的靶细胞，并介导细胞间的信息交换。在这项研究中，我们的目的是调查是否外泌体衍生的miRNA介导上皮间充质细胞通信相关的肾纤维化后的UIRI。结果表明，在缺氧条件下，大鼠肾小管上皮细胞（NRK-52 E）分泌的外泌体明显增加。通过Rab 27 a敲除或GW 4869处理抑制外泌体分泌改善了体内UIRI后的肾纤维化。从NRK-52 E细胞经缺氧处理后纯化的exosomes可以激活大鼠肾成纤维细胞（NRK-49 F）。通过Rab 27 a敲低或GW 4869处理来抑制缺氧NRK-52 E细胞中的外泌体分泌消除了NRK-49 F细胞活化。有趣的是，外泌体miRNA阵列分析显示，与对照组相比，缺氧后miR-150- 5 p表达增加。抑制外泌体miR-150- 5 p在体外消除了缺氧NRK-52 E细胞促进NRK-49 F细胞活化的能力，注射来自缺氧NRK-52 E细胞的富含miR-150- 5 p的外泌体加重了UIRI后的肾纤维化，并且在体内通过miR-150- 5 p缺陷的外泌体减轻了UIRI后的肾纤维化。此外，肾小管细胞来源的exosomal miR-150- 5 p可以负调控细胞因子信号转导抑制因子1的表达，从而激活成纤维细胞。因此，我们的研究结果表明，阻断外泌体miR-150- 5 p介导的肾小管上皮细胞-成纤维细胞通讯可能提供一种新的治疗靶点，以防止UIRI进展为肾纤维化。
Unilateral ischemia reperfusion injury (UIRI) with longer ischemia time is associated with an increased risk of acute renal injury and chronic kidney disease. Exosomes can transport lipid, protein, mRNA, and miRNA to corresponding target cells and mediate intercellular information exchange. In this study, we aimed to investigate whether exosome-derived miRNA mediates epithelial-mesenchymal cell communication relevant to renal fibrosis after UIRI. The secretion of exosomes increased remarkably in the kidney after UIRI and in rat renal tubular epithelium cells (NRK-52E) after hypoxia treatment. The inhibition of exosome secretion by Rab27a knockout or GW4869 treatment ameliorates renal fibrosis following UIRI in vivo. Purified exosomes from NRK-52E cells after hypoxia treatment could activate rat kidney fibroblasts (NRK-49F). The inhibition of exosome secretion in hypoxic NRK-52E cells through Rab27a knockdown or GW4869 treatment abolished NRK-49F cell activation. Interestingly, exosomal miRNA array analysis revealed that miR-150-5p expression was increased after hypoxia compared with the control group. The inhibition of exosomal miR-150-5p abolished the ability of hypoxic NRK-52E cells to promote NRK-49F cell activation in vitro, injections of miR-150-5p enriched exosomes from hypoxic NRK-52E cells aggravated renal fibrosis following UIRI, and renal fibrosis after UIRI was alleviated by miR-150-5p-deficient exosome in vivo. Furthermore, tubular cell-derived exosomal miR-150-5p could negatively regulate the expression of suppressor of cytokine signaling 1 to activate fibroblast. Thus, our results suggest that the blockade of exosomal miR-150-5p mediated tubular epithelial cell-fibroblast communication may provide a novel therapeutic target to prevents UIRI progression to renal fibrosis.
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影响因子：
3.7
作者：
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