Ogawa Daisuke, Eguchi Jun, Wada Jun, Terami Naoto, Hatanaka Takashi, Tachibana Hiromi, Nakatsuka Atsuko, Horiguchi Chikage Sato, Nishii Naoko, Makino Hirofumi
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan ; Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
PLoS One. 2014 Jan 22;9(1):e85594. doi: 10.1371/journal.pone.0085594. eCollection 2014.
Nuclear hormone receptors (NHRs) are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ) and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN), the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m), and cell lines of mesangial (MES13), podocyte (MPC), proximal tubular epithelial (mProx24) and collecting duct (mIMCD3) origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77), nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN.
核激素受体（NHRs）是调节碳水化合物和脂质代谢、免疫反应及炎症的转录因子。尽管包括过氧化物酶体增殖物激活受体γ（PPARγ）和PPARα在内的几种NHRs在糖尿病肾病（DN）中显示出肾脏保护作用，但其他NHRs在肾脏中的表达和作用仍未得到认识。为了研究NHRs在肾脏生物学中的潜在作用，我们使用定量实时聚合酶链反应来分析小鼠NHR超家族的所有49个成员在小鼠肾脏组织（C57BL/6和db/m）以及在正常和高糖条件下源自系膜（MES13）、足细胞（MPC）、近端肾小管上皮（mProx24）和集合管（mIMCD3）的细胞系中的表达情况。在C57BL/6小鼠肾细胞中，肝细胞核因子4α、鸡卵清蛋白上游启动子转录因子II（COUP-TFII）和COUP-TFIII高度表达。在高血糖期间，包括神经元衍生克隆77（Nur77）、核受体相关因子1和神经元衍生孤儿受体1在内的NHR 4A亚组的表达在糖尿病C57BL/6和db/db小鼠中显著增加。在肾细胞系中，PPARδ在系膜和近端肾小管上皮细胞中高度表达，而COUP-TFs在足细胞、近端肾小管上皮细胞和集合管细胞中高度表达。高糖条件增加了系膜和集合管细胞中Nur77的表达以及足细胞中肝X受体α的表达。这些数据证明了NHR在小鼠肾细胞和培养的肾细胞系中的表达，并提示了肾脏中治疗DN的潜在治疗靶点。
