Department of Endocrinology, Chinese PLA 903rd Hospital (Former Chinese PLA 117th Hospital), Hangzhou, 310013, China.
Divison of Health Services, Chinese PLA 903rd Hospital (Former Chinese PLA 117th Hospital), Hangzhou, 310013, China.
Endocr J. 2019 Nov 28;66(11):1029-1037. doi: 10.1507/endocrj.EJ19-0017. Epub 2019 Aug 1.
In the present study, we investigate the effect of reduced cystathionine-γ-lyase (CSE) expression in high glucose induced metalloproteinases14 (MMP14) expression in adipocytes and visceral adipose tissues. Diabetic mice were prepared by injections of STZ and the expression of CSE, MMP14 in visceral adipose tissues were determined. Adipocytes were differentiated from 3T3-L1 cells and treated with high glucose (HG), HS slow-releasing compound GYY4137 or transfected with CSE siRNA. Then the expression of CSE, MMP14 were determined by western blotting. CSE knockout mice were generated by crossing CSE heterozygous mice and given intraperitoneally (i.p.) injections of GYY4137, and then the expression of CSE and MMP14 in visceral adipose tissues were determined by quantitative real-time PCR and western blotting. The following results were obtained from the study. In adipose tissues of diabetic mice, the mRNA and protein expression of MMP14 increased while the mRNA and protein expression of CSE decreased. In 3T3-L1 adipocytes, both HG DMEM and CSE siRNA transfection increased the mRNA and protein of MMP14. The addition of GYY4137 inhibited HG-induced upregulation of MMP14 expression. In CSE knockout mice, the mRNA and protein expression of MMP14 in adipose tissues increased, which could be inhibited by i.p. injections of GYY4137. In conclusion, high glucose increased the expression of MMP14 in adipocytes and visceral adipose tissues through inhibiting the expression of CSE.
在本研究中,我们研究了低胱硫醚-γ-裂解酶(CSE)表达减少对高糖诱导脂肪细胞和内脏脂肪组织中金属蛋白酶 14(MMP14)表达的影响。通过注射链脲佐菌素(STZ)制备糖尿病小鼠,并测定内脏脂肪组织中 CSE、MMP14 的表达。将 3T3-L1 细胞分化为脂肪细胞,并用高葡萄糖(HG)、HS 慢释放化合物 GYY4137 或 CSE siRNA 转染处理。然后通过 Western blot 测定 CSE、MMP14 的表达。通过将 CSE 杂合子小鼠杂交并经腹腔(i.p.)注射 GYY4137 生成 CSE 敲除小鼠,然后通过定量实时 PCR 和 Western blot 测定内脏脂肪组织中 CSE 和 MMP14 的表达。研究结果如下。在糖尿病小鼠的脂肪组织中,MMP14 的 mRNA 和蛋白表达增加,而 CSE 的 mRNA 和蛋白表达减少。在 3T3-L1 脂肪细胞中,HG DMEM 和 CSE siRNA 转染均增加了 MMP14 的 mRNA 和蛋白。GYY4137 的添加抑制了 HG 诱导的 MMP14 表达上调。在 CSE 敲除小鼠中,脂肪组织中 MMP14 的 mRNA 和蛋白表达增加,腹腔注射 GYY4137 可抑制其增加。总之,高葡萄糖通过抑制 CSE 的表达增加了脂肪细胞和内脏脂肪组织中 MMP14 的表达。