Abstract：
UNASSIGNED: Polycystic ovarian syndrome (PCOS) is a prevalent metabolic and endocrine condition in females of reproductive age. This work was to discover the underlying role of Dickkopf 1 (DKK1) and its putative regulating mechanism in P COS.
UNASSIGNED: Mice recieved dehydroepiandrosterone (DHEA) injection to establish the in vivo P COS model.Hematoxylin and eosin (H&E) staining was performed for histological analysis. RT-qP CR and Western blotting were used to detect gene and protein expression. CCK-8 and flow cytometry assays were applied to detect cell viability and apoptosis. Co-immunoprecipitation (Co-IP) and immunoprecipitation (IP) were applied to assess association between DKK1 and SIRT2.
UNASSIGNED: In this work, DKK1 is downregulated in P COS rats. It was revealed that DKK1 knockdown induced apoptosis and suppressed proliferation in KGN cells, whereas DKK1 overexpression had exactly the opposite effects. In addition, DKK1 deactivates the T GF-β1/SMad3 signaling pathway, thereby controlling KGN cell proliferation and apoptosis. Besides, SIRT2 inhibition reversed the impact of DKK1 overexpression on KGN cell proliferation and apoptosis. Furthermore, SIRT2 downregulated DKK1 expression by deacetylating DKK1 in KGN cells.
UNASSIGNED: Altogether, we concluded that SIRT2-induced deacetylation of DKK1 triggers T GF-β1/Smad3 hyperactivation, thereby inhibiting proliferation and promoting apoptosis of KGN cells. The above results indicated that DKK1 might function as a latent target for P COS treatment.
UNASSIGNED: Mice recieved dehydroepiandrosterone (DHEA) injection to establish the in vivo P COS model.Hematoxylin and eosin (H&E) staining was performed for histological analysis. RT-qP CR and Western blotting were used to detect gene and protein expression. CCK-8 and flow cytometry assays were applied to detect cell viability and apoptosis. Co-immunoprecipitation (Co-IP) and immunoprecipitation (IP) were applied to assess association between DKK1 and SIRT2.
UNASSIGNED: In this work, DKK1 is downregulated in P COS rats. It was revealed that DKK1 knockdown induced apoptosis and suppressed proliferation in KGN cells, whereas DKK1 overexpression had exactly the opposite effects. In addition, DKK1 deactivates the T GF-β1/SMad3 signaling pathway, thereby controlling KGN cell proliferation and apoptosis. Besides, SIRT2 inhibition reversed the impact of DKK1 overexpression on KGN cell proliferation and apoptosis. Furthermore, SIRT2 downregulated DKK1 expression by deacetylating DKK1 in KGN cells.
UNASSIGNED: Altogether, we concluded that SIRT2-induced deacetylation of DKK1 triggers T GF-β1/Smad3 hyperactivation, thereby inhibiting proliferation and promoting apoptosis of KGN cells. The above results indicated that DKK1 might function as a latent target for P COS treatment.
摘要：
■多囊卵巢综合征（PCOS）是育龄女性普遍存在的代谢和内分泌疾病。这项工作是为了发现Dickkopf1（DKK1）的潜在作用及其在PCOS中的推定调节机制。
■小鼠注射脱氢表雄酮（DHEA）建立体内PCOS模型。进行苏木精和伊红(H&E)染色用于组织学分析。RT-qPCR和Westernblotting用于检测基因和蛋白质表达。应用CCK-8和流式细胞术检测细胞活力和凋亡。应用免疫共沉淀(Co-IP)和免疫共沉淀(IP)来评估DKK1和SIRT2之间的关联。
■在这项工作中，DKK1在PCOS大鼠中下调。发现DKK1敲低诱导KGN细胞凋亡和抑制增殖,而DKK1过表达具有完全相反的作用。此外,DKK1使TGF-β1/SMad3信号通路失活，从而控制KGN细胞增殖和凋亡。此外,SIRT2抑制逆转了DKK1过表达对KGN细胞增殖和凋亡的影响。此外，SIRT2通过使KGN细胞中的DKK1脱乙酰而下调DKK1的表达。
■总之，我们得出的结论是SIRT2诱导的DKK1脱乙酰触发TGF-β1/Smad3过度激活，从而抑制KGN细胞的增殖并促进其凋亡。以上结果表明，DKK1可能是PCOS治疗的潜在靶标。
■小鼠注射脱氢表雄酮（DHEA）建立体内PCOS模型。进行苏木精和伊红(H&E)染色用于组织学分析。RT-qPCR和Westernblotting用于检测基因和蛋白质表达。应用CCK-8和流式细胞术检测细胞活力和凋亡。应用免疫共沉淀(Co-IP)和免疫共沉淀(IP)来评估DKK1和SIRT2之间的关联。
■在这项工作中，DKK1在PCOS大鼠中下调。发现DKK1敲低诱导KGN细胞凋亡和抑制增殖,而DKK1过表达具有完全相反的作用。此外,DKK1使TGF-β1/SMad3信号通路失活，从而控制KGN细胞增殖和凋亡。此外,SIRT2抑制逆转了DKK1过表达对KGN细胞增殖和凋亡的影响。此外，SIRT2通过使KGN细胞中的DKK1脱乙酰而下调DKK1的表达。
■总之，我们得出的结论是SIRT2诱导的DKK1脱乙酰触发TGF-β1/Smad3过度激活，从而抑制KGN细胞的增殖并促进其凋亡。以上结果表明，DKK1可能是PCOS治疗的潜在靶标。
