Detection of serum lactate dehydrogenase A and its metabolites on placental function in patients with intrahepatic cholestasis of pregnancy

IF 4.8 2区 医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-01-03 DOI:10.1016/j.intimp.2024.113739
Huan Huang , Jianyi Gao , Ruirui Dong , Rong Wang , Ling Li , Gaoying Wang , Yingxian Shi , Kailin Luo , Jing Chen , Wenqing Yuan , Xiaoxue Tian , Haijian Zhao , Ting Zhang
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Abstract

A specific liver disease during pregnancy is intrahepatic cholestasis of pregnancy (ICP). The current clinical diagnosis mainly depends on the level of serum total bile acid (TBA), which lacks sensitivity and specificity. Lactate dehydrogenase A (LDHA) is a new biomarker highly expressed in the serum of ICP patients, which was screened by data-independent acquisition (DIA) proteomic technology in our previous studies. There is currently a lack of a rapid, quantitative, and sensitive detection method to measure LDHA levels in serum. This study aimed to establish a time-resolved fluorescent nanomicrospheres immunochromatographic test strip to detect LDHA in serum and evaluate its value in clinical diagnosis and treatment of ICP. Subsequently, the mechanism of LDHA in mediating the inflammatory of ICP was explored in vitro. In vitro, taurocholic acid (TCA) at a concentration of 100 μM was used to simulate an ICP environment. The AKT/mTOR/HIF-1α signaling pathway was activated in TCA-treated HTR-8/SVeno cells, leading to an increase in LDHA levels. The lactic acid produced by LDHA-mediated glycolytic metabolism may be related to the regulation of inflammation in placental trophoblast cells. According to these findings, LDHA could be a new target that provide promising ideas for the diagnosis, prediction and treatment of ICP.

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妊娠肝内胆汁淤积症患者血清乳酸脱氢酶A及其代谢物对胎盘功能的影响。
妊娠期肝内胆汁淤积(ICP)是一种特殊的肝脏疾病。目前临床诊断主要依靠血清总胆汁酸(TBA)水平,缺乏敏感性和特异性。乳酸脱氢酶A (Lactate dehydrogenase A, LDHA)是我们在前期研究中通过数据独立获取(data-independent acquisition, DIA)蛋白质组学技术筛选出的在ICP患者血清中高表达的新生物标志物。目前缺乏一种快速、定量、灵敏的检测血清中LDHA水平的方法。本研究旨在建立一种时间分辨荧光纳米微球免疫层析试纸条检测血清中的LDHA,并评价其在临床诊断和治疗ICP中的价值。随后,我们通过体外实验探讨了LDHA介导ICP炎症的机制。体外采用100 μM的牛磺胆酸(TCA)模拟ICP环境。在tca处理的HTR-8/SVeno细胞中,AKT/mTOR/HIF-1α信号通路被激活,导致LDHA水平升高。ldha介导的糖酵解代谢产生的乳酸可能与胎盘滋养细胞炎症的调节有关。由此可见,LDHA为ICP的诊断、预测和治疗提供了新的靶点。
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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