Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, Wroclaw, Poland.
Laboratory of Gene Expression, Institute of Biotechnology CAS, Biocev, Vestec, Czech Republic.
J Cell Mol Med. 2023 Apr;27(7):927-938. doi: 10.1111/jcmm.17694. Epub 2023 Mar 1.
The β-lactoglobulin (β-LG) was previously characterized as a mild antioxidant modulating cell viability. However, its biological action regarding endometrial stromal cell cytophysiology and function has never been considered. In this study, we investigated the influence of β-LG on the cellular status of equine endometrial progenitor cells under oxidative stress. The study showed that β-LG decreased the intracellular accumulation of reactive oxygen species, simultaneously ameliorating cell viability and exerting an anti-apoptotic effect. However, at the transcriptional level, the reduced mRNA expression of pro-apoptotic factors (i.e. BAX and BAD) was accompanied by decreased expression of mRNA for anti-apoptotic BCL-2 and genes coding antioxidant enzymes (CAT, SOD-1, GPx). Still, we have also noted the positive effect of β-LG on the expression profile of transcripts involved in endometrial viability and receptivity, including ITGB1, ENPP3, TUNAR and miR-19b-3p. Finally, the expression of master factors of endometrial decidualization, namely prolactin and IGFBP1, was increased in response to β-LG, while non-coding RNAs (ncRNAs), that is lncRNA MALAT1 and miR-200b-3p, were upregulated. Our findings indicate a novel potential role of β-LG as a molecule regulating endometrial tissue functionality, promoting viability and normalizing the oxidative status of endometrial progenitor cells. The possible mechanism of β-LG action includes the activation of ncRNAs essential for tissue regeneration, such as lncRNA MALAT-1/TUNAR and miR-19b-3p/miR-200b-3p.
β-乳球蛋白（β-LG）先前被描述为一种温和的抗氧化剂，可调节细胞活力。然而，其关于子宫内膜基质细胞细胞生理学和功能的生物学作用尚未被考虑。在这项研究中，我们研究了β-LG 在氧化应激下对马子宫内膜祖细胞细胞状态的影响。研究表明，β-LG 减少了活性氧物质的细胞内积累，同时改善了细胞活力并发挥了抗凋亡作用。然而，在转录水平上，促凋亡因子（即 BAX 和 BAD）的 mRNA 表达减少伴随着抗凋亡 BCL-2 和编码抗氧化酶（CAT、SOD-1、GPx）的基因的 mRNA 表达减少。尽管如此，我们还注意到 β-LG 对与子宫内膜活力和接受性相关的转录本表达谱的积极影响，包括 ITGB1、ENPP3、TUNAR 和 miR-19b-3p。最后，β-LG 还增加了子宫内膜蜕膜化的主要调节因子，即催乳素和 IGFBP1 的表达，而非编码 RNA（ncRNA），即 lncRNA MALAT1 和 miR-200b-3p，也被上调。我们的研究结果表明，β-LG 作为一种调节子宫内膜组织功能的分子具有新的潜在作用，促进了细胞活力并使子宫内膜祖细胞的氧化状态正常化。β-LG 作用的可能机制包括激活对组织再生至关重要的 ncRNA，如 lncRNA MALAT-1/TUNAR 和 miR-19b-3p/miR-200b-3p。
