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Decreased shedding dipeptidyl peptidase 4 from membrane in Hashimoto's thyroiditis.

桥本氏甲状腺炎细胞膜二肽基肽酶 4 脱落减少。

  • 影响因子:3.32
  • DOI:10.1016/j.intimp.2020.106315
  • 作者列表:"Xu W","Liu Y","Cheng X","Huang N","Hou N","Wang H","Han F","Han X","Sun X
  • 发表时间:2020-02-18

AIMS:This study aimed to determine the concentration and enzymatic activity of dipeptidyl peptidase 4 (DPP4) in serum and peripheral blood mononuclear cells (PBMCs) from patients with Hashimoto's thyroiditis (HT) and to explore the potential mechanism of the abnormal DPP4 in HT development. METHODS:A total of 33 newly diagnosed HT patients and 31 age- and sex-matched healthy controls were enrolled. Clinical characteristics and thyroid function data were collected for all participants. Serum DPP4 and kallikrein-related peptidase 5 (KLK5) concentrations were measured by sandwich enzyme-linked immunosorbent assay. DPP4 enzymatic activities in serum and PBMCs were determined by enzymatic assay. DPP4, KLK5 and interferon (IFN)-γ mRNA expression levels in PBMCs were evaluated by quantitative real-time polymerase chain reaction. RESULTS:Serum DPP4 level and activity were significantly lower in the HT group compared with the control group. However, DPP4 mRNA expression was significantly increased and both serum KLK5 concentration and KLK5 mRNA expression in PBMCs were significantly decreased in HT patients. Correlation analyses revealed that DPP4 concentration was positively correlated with DPP4 enzymatic activity in serum. No significant difference in DPP4 activity was found in PBMCs. DPP4 enzymatic activity in PBMCs was negatively correlated with DPP4 enzymatic activity in serum. IFN-γ mRNA expression in PBMCs was significantly increased in HT patients. CONCLUSIONS:DPP4 is involved in the development and pathological process of HT. Decreased cleavage of membrane-anchored DPP4 by KLK5 may be responsible for the decreased serum DPP4 levels in HT patients.


目的: 本研究旨在测定桥本甲状腺炎 (HT) 患者血清和外周血单个核细胞 (pbmc) 中二肽基肽酶 4 (DPP4) 的浓度和酶活性并探讨 DPP4 异常在 HT 发生发展中的潜在机制。 方法: 共纳入 33 例新诊断的 HT 患者和 31 例年龄和性别匹配的健康对照。收集所有参与者的临床特征和甲状腺功能数据。采用夹心酶联免疫吸附法测定血清 DPP4 和激肽释放酶相关肽酶 5 (KLK5) 浓度。采用酶法测定血清和 pbmc 中 DPP4 酶活性。通过定量实时聚合酶链反应评价 pbmc 中 DPP4 、 KLK5 和干扰素 (IFN)-γ mRNA 表达水平。 结果: 与对照组相比,HT 组血清 DPP4 水平和活性显著降低。然而,HT 患者 DPP4 mRNA 表达显著升高,血清 KLK5 浓度和 PBMCs 中 KLK5 mRNA 表达均显著降低。相关分析表明,血清中 DPP4 浓度与 DPP4 酶活性呈正相关。在 pbmc 中未发现 DPP4 活性的显著差异。PBMCs 中 DPP4 酶活性与血清中 DPP4 酶活性呈负相关。HT 患者 PBMCs 中 IFN-γ mRNA 表达明显升高。 结论: DPP4 参与了 HT 的发生发展及病理过程。KLK5 对膜锚定 DPP4 的裂解减少可能是 HT 患者血清 DPP4 水平降低的原因。



作者列表:["Travaglino A","Pace M","Varricchio S","Insabato L","Giordano C","Picardi M","Pane F","Staibano S","Mascolo M"]

METHODS:OBJECTIVES:To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS:Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS:Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS:Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.

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作者列表:["Lee, Inhwa","Kim, Hyeung Kyoo","Soh, Euy Young","Lee, Jeonghun"]

METHODS:Background Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. Methods Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. Results In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. Conclusions The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.

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作者列表:["Zhang Z","Xu T","Qin W","Huang B","Chen W","Li S","Li J"]

METHODS::PTPN2 is one of the members of the protein Tyrosine Phosphatases (PTPs) family. To explore the promotive effect of upregulated PTPN2 induced by inflammatory response or oxidative stress on the progression of thyroid cancer. PTPN2 level in thyroid cancer tissues and cell lines was detected. Kaplan-Meier method was applied for evaluating the prognostic value of PTPN2 in thyroid cancer patients. After stimulation of inflammatory response (treatment of IFN-γ and TNF-α), or oxidative stress (treatment of H2O2), protein level of PTPN2 in K1 cells was measured by Western blot. Regulatory effects of PTPN2 on EdU-positive staining and Ki-67 positive cell ratio in K1 cells either with H2O2 stimulation or not were determined. PTPN2 was upregulated in thyroid cancer tissues and cell lines. Its level was higher in metastatic thyroid cancer patients than those of non-metastatic ones. High level of PTPN2 predicted worse prognosis of thyroid cancer. Treatment of either IFN-γ or TNF-α upregulated protein level of PTPN2 in K1 cells. Meanwhile, H2O2 stimulation upregulated PTPN2, which was reversed by NAC administration. With the stimulation of increased doses of H2O2, EdU-positive staining and Ki-67 positive cell ratio were dose-dependently elevated. Silence of PTPN2 attenuated proliferative ability and Ki-67 expression in K1 cells either with H2O2 stimulation or not. Inflammatory response or oxidative stress induces upregulation of PTPN2, thus promoting the progression of thyroid cancer.

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