Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats
Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats
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颗粒体蛋白前体在慢性牙周炎患者中高表达，可预防大鼠实验性牙周炎
DOI：
10.1002/jper.18-0132
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发表时间：
2018-12-01
影响因子：
4.3
通讯作者：
Yang, Pishan
中科院分区：
文献类型：
--
作者：
Li, Xiao;Zuo, Zhibin;Yang, Pishan
背景自分泌生长因子颗粒蛋白前体（PGRN）在机体的生理和病理过程中起着重要作用。然而，其在慢性牙周炎（CP）中的作用尚不清楚。方法收集45例CP患者和43例健康对照者。分别采用逆转录-定量聚合酶链反应（RT-qPCR）和免疫组化法检测牙龈活检组织中PGRN的表达。采用ELISA法对牙周非手术治疗前后龈沟液（GCF）中PGRN、肿瘤坏死因子α（TNF-α）和白细胞介素-1 β（IL-1 β）的水平进行定量。此外，将重组人PGRN（rhPGRN）或其载体注射到结扎诱导的实验性牙周炎大鼠的牙龈中，以测试其对疾病过程的影响。通过组织形态计量学分析评估局部炎性细胞浸润和牙槽骨丢失，并通过RT-qPCR和ELISA测定牙龈中TNF-α和IL-1 β的表达水平。与健康对照组相比，CP患者牙龈和GCF中的PGRN表达增加。随着牙周临床指标的下降，非手术治疗后1个月龈沟液中PGRN与TNF-α的摩尔比显著高于基线（35.31 ± 22.09 vs 25.67 ± 16.19，P < 0.01）。在实验性牙周炎大鼠中，局部施用rhPGRN与赋形剂治疗组相比减轻炎性细胞浸润（P < 0.05），抑制牙槽骨丢失（P < 0.05），并且降低TNF-α和IL-1 β水平（均P < 0.01）。结论颗粒蛋白前体在CP患者牙龈和GCF中高度表达，对大鼠实验性牙周炎具有保护作用。
Background The autocrine growth factor progranulin (PGRN) plays a crucial role in the physiological and pathological processes. However, its function in chronic periodontitis (CP) remains unclear. Methods Results Forty-five CP patients and 43 healthy controls were recruited. Expressions of PGRN in gingival biopsies were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry, respectively. The levels of PGRN, tumor necrosis factor alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) in the gingival crevicular fluid (GCF) before and after non-surgical periodontal treatment were quantified by ELISA. In addition, recombinant human PGRN (rhPGRN) or its vehicle was injected into the gingiva of rats with ligature-induced experimental periodontitis to test its influence on the disease process. Local inflammatory cell infiltration and alveolar bone loss were assessed by histomorphometric analysis, and the expression levels of TNF-alpha and IL-1 beta in the gingiva were determined by RT-qPCR and ELISA. PGRN expression was increased in the gingiva and GCF of patients with CP compared with healthy controls. With the decline of periodontal clinical indices, the molar ratio of PGRN to TNF-alpha in GCF at 1 month after non-surgical treatment was significantly higher than at baseline (35.31 +/- 22.09 vs 25.67 +/- 16.19, P < 0.01). In rats with experimental periodontitis, local administration of rhPGRN attenuated inflammatory cell infiltration (P < 0.05), inhibited alveolar bone loss (P < 0.05) and decreased TNF-alpha and IL-1 beta levels (both P < 0.01) compared with the vehicle treatment group. Conclusion These findings suggest that progranulin is highly expressed in the gingiva and GCF of patients with CP and protects against experimental periodontitis in rats.