Over proliferation of glomerular mesangial cells (MCs) disturbs mesangial homeostasis and leads to renal damage in mesangioproliferative glomerulonephritis. It is documented that transcriptional factors may be involved in the proliferation of MCs. This study aims to identify the key transcriptional factor that prevents the MCs from over proliferation and to clarify its regulatory mechanism. Microarray analysis of glomeruli isolated from Sprague-Dawley rats (SD rats) with or without anti-Thy1 nephritis (anti-Thy1N) showed that the cell cycle pathway was the most enriched pathway in anti-Thy1N model, and the D-site binding protein (DBP) ranked first in the cluster of transcription factors. Compare with normal rats, DBP is markedly decreased accompanied by an over proliferation of MCs in rats with anti-Thy1N. The cell proliferative capacity was measured by 5-Ethynyl-2'-deoxyuridine (EdU) assay in primary rat MCs with DBP knockdown or overexpression, respectively. The results showed that the knockdown of DBP significantly promoted the proliferation of MCs, whereas the overexpression of DBP inhibited the MCs' proliferation, compared to that of the control cells. Further study indicated that DBP arrested G1/S-phase transition by inhibiting the expression of p21, p27 and inducing the Cyclin D1 expression in MCs. The current data suggest that DBP effectively inhibits the proliferation of MCs through G1 phase arrest, and the decrease of DBP may induce mesangial over proliferation in rats with anti-Thy1N.

中文翻译：

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D-位点结合蛋白通过介导大鼠系膜细胞的细胞周期进程来调节细胞增殖。

肾小球系膜细胞（MCs）过度增殖会干扰肾小球系膜稳态，并导致肾血管性增生性肾小球肾炎的肾损害。据记载，转录因子可能参与MC的增殖。这项研究旨在确定防止MC过度增殖的关键转录因子，并阐明其调控机制。从有或没有抗Thy1肾炎（anti-Thy1N）的Sprague-Dawley大鼠（SD大鼠）分离的肾小球的微阵列分析表明，细胞周期途径是抗Thy1N模型中最富集的途径，且D位点结合蛋白（DBP）在转录因子簇中排名第一。与正常大鼠相比，抗Thy1N大鼠的DBP明显降低，而MC过度增殖。通过5-乙炔基-2'-脱氧尿苷（EdU）测定分别在具有DBP抑制或过表达的原代大鼠MC中测量细胞的增殖能力。结果表明，与对照细胞相比，敲除DBP显着促进了MCs的增殖，而DBP的过表达抑制了MCs的增殖。进一步的研究表明，DBP通过抑制p21，p27的表达并诱导MCs中cyclin D1的表达来阻止G1 / S期的过渡。目前的数据表明，DBP可通过G1期阻滞有效抑制MCs的增殖，而DBP的降低可能导致抗Thy1N大鼠系膜过度增殖。结果表明，与对照细胞相比，敲除DBP显着促进了MCs的增殖，而DBP的过表达抑制了MCs的增殖。进一步的研究表明，DBP通过抑制p21，p27的表达并诱导MCs中cyclin D1的表达来阻止G1 / S期的过渡。目前的数据表明，DBP可通过G1期阻滞有效抑制MCs的增殖，而DBP的降低可能导致抗Thy1N大鼠系膜过度增殖。结果表明，与对照细胞相比，敲除DBP显着促进了MCs的增殖，而DBP的过表达抑制了MCs的增殖。进一步的研究表明，DBP通过抑制p21，p27的表达并诱导MCs中cyclin D1的表达来阻止G1 / S期的过渡。目前的数据表明，DBP可通过G1期阻滞有效抑制MCs的增殖，而DBP的降低可能导致抗Thy1N大鼠系膜过度增殖。p27并诱导MC中Cyclin D1的表达。目前的数据表明，DBP可通过G1期阻滞有效抑制MCs的增殖，而DBP的降低可能导致抗Thy1N大鼠系膜过度增殖。p27并诱导MC中Cyclin D1的表达。目前的数据表明，DBP可通过G1期阻滞有效抑制MCs的增殖，而DBP的降低可能导致抗Thy1N大鼠系膜过度增殖。