Estrogen inhibits glomerular epithelial protein 1 to promote proliferation of podocytes in kidney of mice
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摘要:
目的 观察雌激素对肾小球足细胞增殖的影响，探讨雌激素在小儿肾病综合症发病中的作用。 方法 用17β-Estradiol（E2）以及其拮抗剂tamoxifen刺激小鼠肾足细胞系MPC5。采用RT-PCR方法检测酪氨酸磷酸酯酶O（PTPRO）mRNA水平的表达。ERα和ERβ过表达载体转染入E2刺激后的MPC5中，RT-PCR检测PTPRO mRNA水平的表达。Western blot检测JAK/STAT信号通路各分子的表达。MTT法检测细胞增殖。 结果 PTPRO的表达随E2剂量的增加而减少，随E2拮抗剂tamoxifen剂量的增加而增加（P<0.05）。当E2结合ERα时，可抑制小鼠肾足细胞中PTPRO表达（P<0.05）。而当E2结合ERβ时，可彻底阻止小鼠肾足细胞中PTPRO表达。PTPRO对JAK1蛋白表达没有影响（P>0.05），可提高JAK2、p-JAK2（Y1007）、STAT3以及 p-STAT3（Y705）蛋白的表达（P<0.05）。E2可促进肾小球足细胞的其增殖，而PTPRO过表达可抑制E2诱导的肾小球足细胞的增殖。 结论 雌激素可通过结合其受体ERα或者ERβ抑制小鼠肾足细胞PTPRO表达, 使JAK/STAT信号通路失活，促进肾小球足细胞增殖。 -
关键词:
- 雌激素 /
- 受体型酪氨酸磷酸酯酶O /
- 肾小球足细胞 /
- 增殖
Abstract:Objective To observe the effect of estrogen on proliferation of podocyte in kidney of mice, explore the role of estrogen in the pathogenesis of childhood nephrotic syndrome. Methods 17β-Estradiol(E2) and its antagonist tamoxifen were used to stimulate mouse kidney podocyte line MPC5, and expression of PTPRO mRNA was tested by RT-PCR. ERα and ERβ overexpression vectors were transfected into E2-stimulated MPC5, and the expression of PTPRO mRNA was detected by RT-PCR. The expressions of molecules in JAK/STAT signal pathway were measured by western blot. Cell proliferation was analyzed by MTT. Results The expression of PTPRO was decreased with the increase of E2 dosage, and was increased with the increase of E2 antagonist tamoxifen dosage. When E2 binds to ERα, it inhibits PTPRO expression in mouse renal podocytes. When E2 binds to ERβ, PTPRO expression in mouse renal podocytes can be completely blocked. PTPRO had no effect on JAK1 protein expression, and increased the expression of JAK2, p-JAK2 (Y1007), STAT3 and p-STAT3 (Y705). E2 can promote glomerular podocyte proliferation, while PTPRO overexpression can inhibit E2-induced proliferation of glomerular podocytes. Conclusion Estrogen inhibits the expression of PTPRO in mouse renal podocytes by binding its receptor ERα or ERβ, inactivates the JAK/STAT signaling pathway and promotes glomerular podocyte proliferation. -
Key words:
- estrogen /
- glomerular epithelial protein 1 /
- glomerular podocytes /
- proliferation
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图 3 PTPRO对JAK/STAT信号通路的影响
A: Western blot检测JAK/STAT信号通路各分子的表达; B: JAK1蛋白表达; C: JAK2蛋白表达; D: p-JAK2(Y1007)蛋白表达; E: STAT3蛋白表达; F: p-STAT3(Y705)蛋白表达.
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