Overexpression of PTPN2 in Visceral Adipose Tissue Ameliorated Atherosclerosis via T Cells Polarization Shift in Diabetic Apoe-/- Mice
Overexpression of PTPN2 in Visceral Adipose Tissue Ameliorated Atherosclerosis via T Cells Polarization Shift in Diabetic Apoe-/- Mice
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内脏脂肪组织中 PTPN2 的过度表达通过糖尿病 Apoe(-/-) 小鼠 T 细胞极化转变改善动脉粥样硬化
DOI：
10.1159/000488415
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Zhong M
中科院分区：
文献类型：
--
作者：
Li Y;Zhou H;Wang F;Han L;Liu M;Li Y;Wang Z;Tang M;Zhang W;Zhong M
背景/目的：脂肪组织中的炎症失调，以促炎T细胞积累增加和调节性T细胞（Treg）减少为标志，有助于糖尿病相关的胰岛素抵抗和动脉粥样硬化。然而，脂肪组织中t细胞介导的炎症的分子机制在很大程度上仍然未知。方法：载脂蛋白E （ApoE-/-）小鼠60只，随机分为饮食组和糖尿病组。高脂高糖饮食联合低剂量链脲佐菌素诱导糖尿病。然后将携带蛋白酪氨酸磷酸酶非受体2型（PTPN2）基因的重组腺病毒转移到ApoE-/-小鼠附睾白色脂肪组织（EWAT）中。转染后，将所有小鼠安乐死，以评估PTPN2对T细胞极化和动脉粥样硬化的影响。结果：糖尿病ApoE-/-小鼠EWAT中PTPN2表达下调。EWAT中PTPN2的过表达逆转了糖尿病小鼠EWAT中Th1/Treg和Th17/Treg的高比值。此外，PTPN2在EWAT中过表达可显著降低巨噬细胞浸润、M1/M2巨噬细胞比例及促炎细胞因子的表达，改善胰岛素抵抗。在主动脉根部病变中，EWAT过表达PTPN2可显著降低易损指数。结论：糖尿病小鼠EWAT中PTPN2过表达可通过T细胞极化转移抑制全身炎症，增加斑块稳定性。
Background/Aims: Dysregulated inflammation in adipose tissue, marked by increased pro-inflammatory T-cell accumulation and reduced regulatory T cells (Treg), contributes to diabetes-associated insulin resistance and atherosclerosis. However, the molecular mechanisms underlying T-cell-mediated inflammation in adipose tissue remain largely unknown. Methods: Sixty apolipoprotein E (ApoE-/-) mice were randomly divided into chow and diabetes groups. Diabetes was induced by a high-fat and high-sugar diet combined with low-dose streptozotocin. Then we transferred a recombinant adenovirus carrying the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene into epididymal white adipose tissue (EWAT) of ApoE-/- mice. After transfection, all mice were euthanized to evaluate the effects of PTPN2 on T cells polarization and atherosclerosis. Results: PTPN2 was downregulated in EWAT of diabetic ApoE-/- mice. PTPN2 overexpression in EWAT reversed the high Th1/Treg and Th17/Treg ratios in EWAT of diabetic mice. In addition, PTPN2 overexpression in EWAT could significantly reduce macrophages infiltration, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines in EWAT, improving insulin resistance. In aortic root lesions, the vulnerability index were significantly decreased by overexpression of PTPN2 in EWAT. Conclusion: These data suggested that PTPN2 overexpression in EWAT would inhibit systemic inflammation and increase the plaque stability via T cells polarization shift in diabetic mice.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0706832104
发表时间：
2007-12-04
影响因子：
11.1
作者：
Tiemessen, Machteld M.;Jagger, Ann L.;Taams, Leonie S.
通讯作者：
Taams, Leonie S.
STAMP2 过度表达可抑制糖尿病小鼠的动脉粥样硬化并稳定斑块
影响因子：
5.3
作者：
Wang J;Han L;Wang ZH;Ding WY;Shang YY;Tang MX;Li WB;Zhang Y;Zhang W;Zhong M
通讯作者：
Zhong M
影响因子：
4.6
作者：
Lee H;Kim M;Baek M;Morales LD;Jang IS;Slaga TJ;DiGiovanni J;Kim DJ
通讯作者：
Kim DJ
影响因子：
7.7
作者：
Hong EG;Ko HJ;Cho YR;Kim HJ;Ma Z;Yu TY;Friedline RH;Kurt-Jones E;Finberg R;Fischer MA;Granger EL;Norbury CC;Hauschka SD;Philbrick WM;Lee CG;Elias JA;Kim JK
通讯作者：
Kim JK