Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis

Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis
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低营养环境引起卵巢子宫内膜异位症基质细胞炎症、细胞增殖和 PGC-1α 表达的变化

DOI:
10.1007/s43032-022-01089-5
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发表时间:
2023
期刊:
Reprod Sci.
影响因子:
--
通讯作者:
Mori T.
Mori T.
中科院分区:
--
文献类型:
--
作者:
Shimura K;Tarumi Y;Fujii M;Ogawa K;Maeda E;Tanaka Y;Okimura H;Kataoka H;Takaoka O;Ito F;Koshiba A;Khan KN;Kusuki I;Kitawaki J;Mori T.

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虽然营养状况在细胞代谢中起重要作用,但其在子宫内膜异位症中的意义尚不清楚。在此,我们研究了低营养微环境对子宫内膜异位症的影响。从卵巢上皮性肿瘤(OESC)和正常子宫内膜(NESC)中分离培养基质细胞(SC)。通过用Hank平衡盐溶液替换培养基来复制低营养微环境。在低营养条件下测定OESC和NESC的增殖。在mRNA和蛋白水平上检测低营养条件下子宫内膜异位症加重因子的表达。在低营养条件下,OESC的增殖能力高于NESC。在OESC中,低营养条件上调血管内皮生长因子(VEGF)、白细胞介素-6和-8、芳香化酶、Bcl-2和过氧化物酶体增殖物激活受体-γ共激活因子-1 α(PGC-1α)的mRNA表达,下调BAX的mRNA表达,并诱导PI. 3、PII和外显子II的转录。Western blotting结果显示,在低营养条件下,VEGF和PGC-1α的表达增加。这些变化与PGC-1α的表达升高相一致,而营养状态补救后PGC-1α在mRNA水平上降低。子宫内膜异位症在试图在低营养微环境下生存时,由于血管生成、炎症、抗凋亡和局部雌激素产生的改变而加重;这可能归因于PGC-1α介导的代谢机制。
Although nutrient status plays an important role in cell metabolism, its significance in endometriosis is obscure. Herein, we investigated the effects of a low-nutrient microenvironment on endometriosis. Stromal cells (SCs) from ovarian endometrioma (OESCs) or normal endometrium without endometriosis (NESCs) were isolated and cultured. A low-nutrient microenvironment was replicated by replacing the culture medium with Hank’s balanced salt solution. OESC and NESC proliferation under the low-nutrient condition was measured. The expression of exacerbating factors in endometriosis under the low-nutrient condition was examined at the mRNA and protein levels. OESCs showed higher proliferation than NESCs under the low-nutrient condition. In OESCs, the low-nutrient condition upregulated the mRNA expression of vascular endothelial growth factor (VEGF), interleukin-6 and -8, aromatase, Bcl-2, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and downregulated that of BAX and induced transcription of PI.3, PII, and exon II. Western blotting revealed elevated VEGF and PGC-1α expression under the low-nutrient condition in OESCs. These changes coincided with the elevated expression of PGC-1α, which was reduced at the mRNA level upon nutrient status rescue. Endometriosis is exacerbated by altered angiogenesis, inflammation, anti-apoptosis, and local estrogen production while trying to survive under a low-nutrient microenvironment; it may be attributed to PGC-1α-mediated metabolic mechanisms.
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