The role of microRNAs (miRNAs) in chronic kidney disease (CKD) is relatively well established, but much less is known about the role(s) of long noncoding RNAs (lncRNAs). Transforming growth factor β1 (TGF-β1) mediates inflammatory and fibrogenic signaling in CKD via the transcription factor Smad3; however, the extent of lncRNAs-based regulation of TGF-β1 signaling in CKD remains unknown. Herein, we identified np_4334, a lncRNA we named Ptprd-IR, whose promoter contains a highly-conserved site for Smad3 binding. Smad3 knockout (KO) eliminated Ptprd-IR upregulation in a murine model of obstructive nephropathy. Furthermore, Ptprd-IR KO in renal tubular epithelial cell cultures blocked TGF-β1- and interleukin-1β (IL-1β)-mediated NF-κB inflammatory signaling but did not impact TGF-β1-triggered Smad3 pathway activity and fibrosis. Accordingly, Ptprd-IR overexpression (OE) upregulated TGF-β1- and IL-1β-mediated NF-κB pathway activation and production of pro-inflammatory cytokines but did not influence TGF-β1-mediated fibrogenic signaling. Additionally, transfection of obstructed kidneys with Ptprd-IR-directed shRNA attenuated the inflammatory response via NF-κB but did not impact TGF-β1/Smad3-mediated fibrogenesis. Overall, our findings demonstrate that the lncRNA Ptprd-IR stimulates the inflammatory response in kidneys and advocate Ptprd-IR as a possible therapeutic target for CKD.

microRNA（miRNA）在慢性肾脏疾病（CKD）中的作用已相对确立，但对长非编码RNA（lncRNA）的作用知之甚少。转化生长因子β1（TGF-β1）通过转录因子Smad3介导CKD中的炎症和纤维生成信号。然而，CKD中基于lncRNAs的TGF-β1信号转导调控的程度仍然未知。在本文中，我们鉴定出np_4334，这是一个我们称为Ptprd-IR的lncRNA，其启动子包含一个高度保守的Smad3结合位点。Smad3基因敲除（KO）消除了梗阻性肾病小鼠模型中Ptprd-IR的上调。此外，肾小管上皮细胞培养物中的Ptprd-IR KO阻断了TGF-β1-和白介素-1β（IL-1β）介导的NF-κB炎症信号，但不影响TGF-β1触发的Smad3途径活性和纤维化。因此，Ptprd-IR过表达（OE）上调了TGF-β1和IL-1β介导的NF-κB途径的激活和促炎性细胞因子的产生，但并未影响TGF-β1介导的纤维化信号。此外，用Ptprd-IR导向的shRNA转染阻塞的肾脏可减轻通过NF-κB的炎症反应，但不影响TGF-β1/ Smad3介导的纤维化。总体而言，我们的发现表明lncRNA Ptprd-IR刺激了肾脏的炎症反应，并提倡Ptprd-IR作为CKD的可能治疗靶标。用Ptprd-IR导向的shRNA转染阻塞性肾脏可减轻通过NF-κB的炎症反应，但不影响TGF-β1/ Smad3介导的纤维化。总体而言，我们的发现表明lncRNA Ptprd-IR刺激了肾脏的炎症反应，并提倡Ptprd-IR作为CKD的可能治疗靶标。用Ptprd-IR导向的shRNA转染阻塞性肾脏可减轻通过NF-κB的炎症反应，但不影响TGF-β1/ Smad3介导的纤维化。总体而言，我们的发现表明lncRNA Ptprd-IR刺激了肾脏的炎症反应，并提倡Ptprd-IR作为CKD的可能治疗靶标。