Abnormal Expression of Prolyl Oligopeptidase (POP) and Its Catalytic Products Ac-SDKP Contributes to the Ovarian Fibrosis Change in Polycystic Ovary Syndrome (PCOS) Mice.
Abnormal Expression of Prolyl Oligopeptidase (POP) and Its Catalytic Products Ac-SDKP Contributes to the Ovarian Fibrosis Change in Polycystic Ovary Syndrome (PCOS) Mice.
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DOI：
10.3390/biomedicines11071927
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发表时间：
2023-07-07
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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多囊卵巢综合征（PCOS）是一种内分泌紊乱和代谢综合征。多囊卵巢综合征的卵巢纤维化病理改变逐渐引起人们的重视。在本研究中，我们通过使用脱氢表雄酮构建PCOS小鼠模型。天狼星红染色显示PCOS小鼠卵巢组织有明显的纤维化。脯氨酰寡肽酶（POP）是一种丝氨酸蛋白酶，其催化产物为N-乙酰丝氨酰赖氨酰脯氨酸（Ac-SDKP）。研究表明POP和Ac-SDKP的异常表达和活性与组织纤维化密切相关。结果表明，POP和Ac-SDKP在PCOS小鼠卵巢中的表达降低。进一步研究表明，POP和Ac-SDKP可促进颗粒细胞基质金属蛋白酶2（MMP-2）的表达，降低转化生长因子β 1（TGF-β1）的表达。高雄激素血症是PCOS的典型症状。结果发现，睾酮可诱导颗粒细胞POP和MMP 2的低表达和TGF-β1的高表达。POP过表达和Ac-SDKP治疗在体外抑制睾酮对TGF-β1和MMP 2的影响，并抑制多囊卵巢综合征小鼠模型中的卵巢纤维化。结论：PCOS患者卵巢组织呈明显纤维化。POP和Ac-SDKP的低表达及纤维化因子的改变参与雄激素诱导的卵巢病理性纤维化。
Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS has gradually attracted people’s attention. In this study, we constructed a PCOS mouse model through the use of dehydroepiandrosterone. Sirius red staining showed that the ovarian tissues in PCOS mice had obvious fibrosis. Prolyl oligopeptidase (POP) is a serine protease and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is its catalytic product. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. It was found that the expression of POP and Ac-SDKP was decreased in the ovaries of PCOS mice. Further studies showed that POP and Ac-SDKP promoted the expression of matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-β1) in granulosa cells. Hyperandrogenemia is a typical symptom of PCOS. We found that testosterone induced the low expression of POP and MMP2 and high expression of TGF-β1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-β1 and MMP2 in vitro and inhibited ovarian fibrosis in the PCOS mouse model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP and Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.
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影响因子：
5.8
作者：
Lewandowski, KC;Komorowski, J;Randeva, HS
通讯作者：
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DOI：
10.1152/ajprenal.00562.2015
发表时间：
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作者：
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