Renal fibrosis is characterized by glomerulosclerosis and tubulointerstitial fibrosis in diabetic nephropathy (DN). We aimed to evaluate the effects of PP2 on renal fibrosis of DN. GSE33744 and GSE86300 were downloaded from the GEO database. Firstly, 839 DEGs were identified between nondiabetic and diabetic mice renal glomerular samples. COX-2 was selected to assess the effects of PP2 on renal glomerulosclerosis. In db/db mice, PP2 decreased the expression of COX-2, phosphorylated p65, and fibrotic proteins, accompanied with attenuated renal glomerulosclerosis. In cultured glomerular mesangial cells, high glucose- (HG-) induced p65 phosphorylation and COX-2 expression were attenuated by PP2 or NF-κB inhibitor PDTC. PP2, PDTC, or COX-2 inhibitor NS-398 ameliorated abnormal proliferation and expression of fibrotic proteins induced by HG. Secondly, 238 DEGs were identified between nondiabetic and diabetic mice renal cortex samples. UCP2 was selected to assess the effects of PP2 on renal tubulointerstitial fibrosis. In db/db mice, PP2 decreased the expression of PPARγ and UCP2, accompanied with attenuated renal tubulointerstitial fibrosis and EMT. In cultured proximal tubular cells, HG-induced PPARγ and UCP2 expression was inhibited by PP2 or PPARγ antagonist GW9662. PP2, GW9662, or UCP2 shRNA ameliorated HG-induced EMT. These results indicated that PP2 ameliorated renal fibrosis in diabetic mice.

中文翻译：

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PP2 通过调节糖尿病小鼠的 NF-κB/COX-2 和 PPARγ/UCP2 通路改善肾纤维化

肾纤维化的特征是糖尿病肾病 (DN) 中的肾小球硬化和肾小管间质纤维化。我们旨在评估 PP2 对 DN 肾纤维化的影响。GSE33744 和 GSE86300 是从 GEO 数据库下载的。首先，在非糖尿病和糖尿病小鼠肾小球样本之间鉴定出 839 个 DEG。选择 COX-2 来评估 PP2 对肾小球硬化的影响。在 db/db 小鼠中，PP2 降低了 COX-2、磷酸化 p65 和纤维化蛋白的表达，伴随着肾小球硬化的减轻。在培养的肾小球系膜细胞中，高糖（HG-）诱导的 p65 磷酸化和 COX-2 表达被 PP2 或 NF- κ减弱B 抑制剂 PDTC。PP2、PDTC 或 COX-2 抑制剂 NS-398 改善了 HG 诱导的纤维化蛋白的异常增殖和表达。其次，在非糖尿病和糖尿病小鼠肾皮质样本之间鉴定出 238 个 DEG。选择 UCP2 来评估 PP2 对肾小管间质纤维化的影响。在 db/db 小鼠中，PP2 降低了 PPAR γ和 UCP2 的表达，并伴有肾小管间质纤维化和 EMT 减弱。在培养的近端肾小管细胞中，HG 诱导的 PPAR γ和 UCP2 表达被 PP2 或 PPAR γ拮抗剂 GW9662 抑制。PP2、GW9662 或 UCP2 shRNA 改善了 HG 诱导的 EMT。这些结果表明PP2改善了糖尿病小鼠的肾纤维化。