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Abstract：
Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-β1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-β1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-β1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.
摘要：
肾纤维化是进行性肾脏疾病中最常见的途径。单侧输尿管梗阻(UUO)模型用于诱导进行性肾纤维化。我们评估了irisin对UUO小鼠肾间质纤维化的影响。从基因表达综合(GEO)数据库下载GSE121190、GSE36496、GSE42303和GSE96101数据集。总的来说,在正常和UUO小鼠肾样品中鉴定出656个差异表达基因(DEGs)。选择骨膜素和基质金属蛋白酶-2（MMP-2）来评估irisin对UUO小鼠肾脏纤维化的影响。在UUO小鼠中，irisin改善肾功能，降低骨膜素和MMP-2的表达，并减轻肾组织中上皮-间质转化和细胞外基质沉积。在HK-2细胞中，irisin治疗可显着减弱TGF-β1诱导的骨膜素和MMP-2的表达。Irisin治疗还抑制TGF-β1诱导的上皮-间质转化，细胞外基质形成，和炎症反应。骨膜素和MMP-2的过表达消除了irisin的这些保护作用。总之,irisin治疗可通过TGF-β1/骨膜素/MMP-2信号通路改善UUO诱导的肾间质纤维化,提示irisin可用于肾间质纤维化的治疗。
