Department of Histology and Embryology, Poznan University of Medical Sciences, 61-781 Poznań, Poland.
Faculty of Exact and Natural Sciences, Institute of Biology, University of Szczecin, 70-415 Szczecin, Poland.
Int J Mol Sci. 2023 Mar 10;24(6):5301. doi: 10.3390/ijms24065301.
Dehydroepiandrosterone (DHEA) is an abundant steroid and precursor of sex hormones. During aging, the reduction in DHEA synthesis causes a significant depletion of estrogens and androgens in different organs, such as the ovaries, brain, and liver. Primary Biliary Cholangitis (PBC) is a cholestatic liver disease that begins with immune-mediated bile duct damage, and is followed by liver fibrosis, and finally, cirrhosis. PBC primarily affects postmenopausal women, with an average age of diagnosis of 65 years, but younger women are also affected. Here, we analyzed the levels of DHEA, estradiol (E2), and estriol (E3) in the PBC sera of females at an age of diagnosis under 40 ( = 37) and above 65 ( = 29). Our results indicate that in PBC patients at an age of diagnosis under 40, E2 was significantly lower compared to that in healthy women. In contrast, the levels of DHEA and E3 were in a normal range. Furthermore, ELISA assays revealed that in PBC patients at an age of diagnosis above 65, the levels of DHEA, E2, and E3 significantly declined in comparison to those in younger patients. In addition, flow cytometry analysis showed that the level of IL-8 significantly decreased while the level of TNF-α increased in older PBC patients compared to younger ones. Moreover, we showed for the first time that the sulfonated form of DHEA, DHEA-S, reduces the levels of both pro-inflammatory interleukins, IL-8 and TNF-α, in PBC-like cholangiocytes (H69-miR506), while it diminishes the level of the pro-fibrotic interleukin, IL-13, in hepatocytes (Hep-G2). Finally, we demonstrated that the expression of the pro-fibrotic agent TGF-β significantly increased in both the early (F0-F3) and cirrhotic (F4) stages of PBC, and this elevation was accompanied by higher α-SMA expression.
去氢表雄酮（DHEA）是一种丰富的类固醇和性激素前体。随着年龄的增长，DHEA 的合成减少会导致不同器官（如卵巢、大脑和肝脏）中的雌激素和雄激素大量消耗。原发性胆汁性胆管炎（PBC）是一种胆汁淤积性肝病，始于免疫介导的胆管损伤，随后发生肝纤维化，最终发展为肝硬化。PBC 主要影响绝经后妇女，平均诊断年龄为 65 岁，但也有年轻女性受到影响。在这里，我们分析了年龄在 40 岁以下（=37）和 65 岁以上（=29）的 PBC 女性患者的 PBC 血清中 DHEA、雌二醇（E2）和雌三醇（E3）的水平。我们的结果表明，在年龄在 40 岁以下的 PBC 患者中，E2 的水平明显低于健康女性。相比之下，DHEA 和 E3 的水平在正常范围内。此外，ELISA 检测显示，在年龄在 65 岁以上的 PBC 患者中，DHEA、E2 和 E3 的水平与年轻患者相比显著下降。此外，流式细胞术分析显示，与年轻患者相比，老年 PBC 患者的白细胞介素-8（IL-8）水平显著降低，而肿瘤坏死因子-α（TNF-α）水平升高。此外，我们首次表明，DHEA 的硫酸化形式 DHEA-S，可降低 PBC 样胆管细胞（H69-miR506）中两种促炎细胞因子 IL-8 和 TNF-α的水平，同时降低肝细胞（Hep-G2）中促纤维化细胞因子 IL-13 的水平。最后，我们证明，在 PBC 的早期（F0-F3）和肝硬化（F4）阶段，促纤维化剂 TGF-β 的表达均显著增加，并且这种升高伴随着更高的α-SMA 表达。
