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马子宫内膜成纤维细胞中前列腺素对基质金属蛋白酶和胶原的影响。

Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts.

机构信息

Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Str 10, 10-748, Olsztyn, Poland.

Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Str 10, 10-748, Olsztyn, Poland.

出版信息

Theriogenology. 2020 Sep 1;153:74-84. doi: 10.1016/j.theriogenology.2020.04.040. Epub 2020 May 11.

Abstract

An increasing number of studies have shown that prostaglandins (PGs) exert multiple regulatory actions in the processes associated to tissue remodeling and fibrosis. Extracellular matrix (ECM) turnover is mediated by matrix metallopeptidases (MMPs). The knowledge about the regulation of their expression in mare endometrium is still limited. Thus, the aim of this study was to investigate whether: (i) profibrotic transforming growth factor (TGF)-β1 modulates PG production in equine endometrium; and (ii) PGE and PGF modulate MMPs, their tissue inhibitors (TIMPs), and collagen 1 (COL1) expression. In experiment 1, the effect of TGF-β1 (5 ng/mL) on PG secretion and PG synthases mRNA transcription, after 24 and 48 h treatment of mare endometrial fibroblast and epithelial cells was investigated using ELISA and qPCR. In experiment 2, the effects of PGE and PGF in doses 10M and 10M on secretion and MMP1, 2, 9, 13, TIMP1, 2, and COL1A1 mRNA transcription in mare endometrial fibroblasts were assessed. Transforming growth factor-β1 treatment decreased secretion of PGF by endometrial fibroblasts (P < 0.05) and PGF and PGE by endometrial epithelial cells (P < 0.05). Prostaglandin E increased MMP-2 and MMP-9, and decreased MMP-13 secretion by endometrial fibroblasts (P < 0.05). Additionally, PGF treatment increased MMP-2, MMP-13 and COL1, but decreased MMP-1 secretion by endometrial fibroblasts (P < 0.05). Prostaglandins may be involved in the processes associated to pathological endometrial remodeling by their effect on MMP expression. The effect of PGF on COL1 secretion from fibroblasts suggests its profibrotic role in pathological endometrial remodeling.

摘要

越来越多的研究表明,前列腺素(PGs)在与组织重塑和纤维化相关的过程中发挥多种调节作用。细胞外基质(ECM)的转化由基质金属蛋白酶(MMPs)介导。关于它们在母马子宫内膜中表达的调节的知识仍然有限。因此,本研究的目的是探讨以下两个问题:(i)促纤维化转化生长因子(TGF)-β1 是否调节马子宫内膜中的 PG 产生;(ii)PGE 和 PGF 是否调节 MMPs、它们的组织抑制剂(TIMPs)和胶原蛋白 1(COL1)的表达。在实验 1 中,使用 ELISA 和 qPCR 研究了 TGF-β1(5ng/mL)在马子宫内膜成纤维细胞和上皮细胞处理 24 和 48 小时后对 PG 分泌和 PG 合酶 mRNA 转录的影响。在实验 2 中,评估了 PGE 和 PGF 在剂量 10M 和 10M 对马子宫内膜成纤维细胞分泌和 MMP1、2、9、13、TIMP1、2 和 COL1A1mRNA 转录的影响。转化生长因子-β1 处理降低了子宫内膜成纤维细胞分泌的 PGF(P<0.05)和子宫内膜上皮细胞分泌的 PGF 和 PGE(P<0.05)。前列腺素 E 增加了 MMP-2 和 MMP-9,并减少了子宫内膜成纤维细胞分泌的 MMP-13(P<0.05)。此外,PGF 处理增加了 MMP-2、MMP-13 和 COL1,但减少了子宫内膜成纤维细胞分泌的 MMP-1(P<0.05)。前列腺素可能通过对 MMP 表达的影响参与与病理性子宫内膜重塑相关的过程。PGF 对成纤维细胞 COL1 分泌的影响表明其在病理性子宫内膜重塑中的促纤维化作用。

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