Abstract：
Diabetic kidney disease (DKD) is a leading cause of kidney failure. However, the involvement of renal fibroblasts and their communications with renal epithelial cells during DKD remain poorly understood. We investigated the potential role of renal proximal tubular epithelial cells (PTECs) in renal fibroblast activation that might lead to DKD. Additionally, the protective effects of curcumin, a known antioxidant, against renal fibroblast activation induced by high glucose-treated PTECs were investigated. Secretome was collected from HK-2 PTECs under normal glucose, high glucose, high glucose pretreated/cotreated with curcumin, or osmotic control condition for 24 h. Such secretome was then used to treat BHK-21 renal fibroblasts for 24 h. BHK-21 cells treated with high glucose-induced secretome had increased levels of fibroblast activation markers, including spindle index, F-actin, α-smooth muscle actin (α-SMA), fibronectin, collagen I, matrix metalloproteinase-2 (MMP-2) and MMP-9, as compared with normal glucose and osmotic control conditions. However, all these increases were successfully mitigated by curcumin. In addition, high glucose markedly increased intracellular reactive oxygen species (ROS) and transforming growth factor-β (TGF-β) secretion, but did not affect the secretion of platelet-derived growth factor A (PDGFA) and interleukin-1β (IL-1β), in HK-2 renal cells as compared with normal glucose and osmotic control conditions. Both intracellular ROS and secreted TGF-β levels were successfully mitigated by curcumin. Therefore, curcumin prevents the high glucose-induced stimulatory effects of renal cell secretome on fibroblast activation, at least in part, via mitigating intracellular ROS and TGF-β secretion.
摘要：
糖尿病肾病（DKD）是肾衰竭的主要原因。然而,DKD期间肾成纤维细胞的参与及其与肾上皮细胞的交流仍知之甚少。我们研究了肾近端肾小管上皮细胞（PTEC）在可能导致DKD的肾成纤维细胞活化中的潜在作用。此外,姜黄素的保护作用,一种已知的抗氧化剂，对高糖处理的PTEC诱导的肾成纤维细胞活化进行了研究。从正常葡萄糖下的HK-2PTEC中收集Secretome，高葡萄糖，高葡萄糖与姜黄素预处理/共混，然后将这种分泌体用于治疗BHK-21肾成纤维细胞24小时。用高葡萄糖诱导的分泌体处理的BHK-21细胞的成纤维细胞活化标志物水平升高，包括主轴指数，F-肌动蛋白,α-平滑肌肌动蛋白（α-SMA），纤连蛋白,胶原蛋白I，与正常葡萄糖和渗透控制条件相比，基质金属蛋白酶2（MMP-2）和MMP-9。然而,姜黄素成功缓解了所有这些增加.此外,高糖显著增加细胞内活性氧（ROS）和转化生长因子-β（TGF-β）的分泌，但不影响血小板源性生长因子A（PDGFA）和白细胞介素-1β（IL-1β）的分泌，与正常葡萄糖和渗透控制条件相比，在HK-2肾细胞中。姜黄素成功地减轻了细胞内ROS和分泌的TGF-β水平。因此,姜黄素可以防止高糖诱导的肾细胞分泌组对成纤维细胞活化的刺激作用，至少在某种程度上,通过减轻细胞内ROS和TGF-β分泌。
