Molecular and Cellular Endocrinology最新文献_第6页

Endocrine Disruptors Chemicals: Impacts of Bisphenol A, Tributyltin and Lead on Thyroid Function

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-22 DOI: 10.1016/j.mce.2025.112467

Glaecir Roseni Mundstock Dias , Andrea Claudia Freitas Ferreira , Leandro Miranda-Alves , Jones Bernardes Graceli , Denise Pires de Carvalho

The large-scale industrial production characteristic of the last century led to an increase in man-made compounds and mobilization of natural compounds, many of which can accumulate in the environment and organisms due to their bioaccumulation and biomagnification properties. The endocrine system is especially vulnerable to these compounds that are known as endocrine disruptor chemicals (EDCs). Thyroid hormones (THs) are essential for normal development and growth, besides being the main regulators of basal metabolic rate. Thus, compounds able to affect THs synthesis, transport, and action could produce important deleterious effects, impacting the development of metabolic and endocrine diseases. Herein, we will review the main effects of EDCs on the thyroid axis, with special emphasis on the widely used substances bisphenol A (BPA), employed in the synthesis of polycarbonate plastics and epoxy resins; tributyltin (TBT), an organotin chemical substance widely used in several agro-industrial applications; and lead (Pb), a ubiquitous environmental and occupational polluting heavy metal. Exposure to these EDCs occurs mainly from the ingestion of contaminated food and beverages. Furthermore, there are few epidemiological studies evaluating human risk, and experimental studies employ different exposure models, making it difficult to integrate results. However, even low doses of these EDCs warn of thyrotoxicity. Since THs homeostasis is essential for health and humans are increasingly being exposed to EDCs, it is important to clarify which substances might act as thyroid hormone system disrupting chemicals and how they act in order to try to overcome their deleterious effects and limit the exposure to these compounds.

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引用次数: 0

Vagotomy suppresses food intake by increasing GLP-1 secretion via the M3 AChR-AMPKα pathway in mice

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-21 DOI: 10.1016/j.mce.2025.112464

Jie Lin , Yikai Shen , Yiwen Xia , Ying Li , Tianlu Jiang , Xusheng Shen , Yiwang Fu , Diancai Zhang , Li Yang , Hao Xu , Zekuan Xu , Linjun Wang

Objective

The gut-brain axis (GBA) is involved in the modulation of multiple physiological activities, and the vagus nerve plays an important role in this process. However, the association between vagus nerve function and nutritional regulation remains unclear. Here, we explored changes in the nutritional status of mice after vagotomy and investigated the underlying mechanisms responsible for these changes.

Methods

We performed vagotomies in mice and verified nerve resection using immunofluorescence staining. We then observed the food intake and body weight of the mice and tested nutritional and inflammation-related markers using enzyme-linked immunosorbent assay (ELISA) kits. The role of glucagon-like peptide 1 (GLP-1) in the GBA was determined using qRT-PCR and ELISA kits. Western blot and ELISA kits were used to explore the underlying mechanisms.

Results

After vagotomy, the mice experienced a deterioration in their nutritional status, which manifested as a significant reduction in body weight and food intake. The expression of the proglucagon gene (GCG), which encodes GLP-1, significantly increased after vagotomy. Mechanistically, acetylcholine (ACh) reversed the HG (high glucose) -induced elevation of GLP-1 secretion. ACh upregulated AMPKα phosphorylation, thereby reducing GLP-1 secretion. Moreover, the level of AMPKα phosphorylation was enhanced by ACh via M3AChR.

Conclusions

ACh released by the vagus nerve counteracts the anorectic effects of GLP-1 under normal physiological conditions. Vagotomy blocks this feedback, resulting in a loss of food intake and body weight in mice.

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引用次数: 0

Loss of chemerin prevents ovariectomy-induced osteoporosis in mice through intraosseous vascular remodeling

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-21 DOI: 10.1016/j.mce.2025.112465

Bingjie Wang , Jinghuai Ni , Lingling Yu , Shuai Chen , Wenbin Shang , Penghua Fang , Wen Min

Chemerin, an adipocyte-secreted adipokine, can regulate bone resorption and bone formation and is a promising therapy for postmenopausal osteoporosis. However, the effect of endogenous chemerin on intraosseous vascular remodeling in postmenopausal osteoporosis remains unclear. In this study, we investigated the effect of chemerin on osteogenesis formation and intraosseous vascular remodeling in ovariectomized Rarres2 knockout (Rarres2^−/−) mice. The results showed that the bone mineral density (BMD) and volume score, trabecular thickness, cortical thickness, bone formation marker BALP and osteocalcin, and angiogenesis markers CD31 and EMCN significantly increased in ovariectomized Rarres2^−/− mice. Furthermore, the expression of biomarkers to osteoblasts (β-catenin and Runx2) and angiogenesis markers (VEGF-A, Noggin, and Ang-1) significantly increased in the bone tissue of ovariectomized Rarres2^−/− mice, as well as in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2^−/− mice. Conversely, treatment with chemerin significantly inhibited expression of biomarkers for osteoblasts and angiogenesis markers in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2^−/− mice. More importantly, the supernatants of the primary intraosseous vascular endothelial cells of the Rarres2^−/− mice could promote the osteogenic differentiation effect of BMSCs, which could be blocked by treating with the chemerin recombinant protein. These data indicate that endogenous chemerin has an inhibitory effect on intraosseous vascular formation as well as osteoblast differentiation and proliferation in ovariectomy-induced osteoporosis mice. Chemerin effectively promoted postmenopausal osteoporosis development, which is associated with the involvement of chemerin in the reduction of microcirculation within the skeleton.

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引用次数: 0

Skeletal muscle disorders as risk factors for type 2 diabetes

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-21 DOI: 10.1016/j.mce.2025.112466

Eshwar R. Tammineni , Carlo Manno , Goldie Oza , Lourdes Figueroa

The incidence and prevalence of muscular disorders and of type 2 diabetes (T2D) is increasing and both represent highly significant healthcare problems, both economically and compromising quality of life. Interestingly, skeletal muscle dysfunction and T2D share some commonalities including dysregulated glucose homeostasis, increased oxidative stress, dyslipidemia, and cytokine alterations. Several lines of evidence have hinted to a relationship between skeletal muscle dysfunction and T2D. For instance, T2D affects skeletal muscle morphology, functionality, and overall health through altered protein metabolism, impaired mitochondrial function, and ultimately cell viability. Conversely, humans suffering from myopathies and their experimental models demonstrated increased incidence of T2D through altered muscle glucose disposal function due to abnormal calcium homeostasis, compromised mitochondrial function, dyslipidemia, increased inflammatory cytokines and fiber size alterations and disproportions. Lifestyle modifications are essential for improving and maintaining mobility and metabolic health in individuals suffering from myopathies along with T2D. In this review, we updated current literature evidence on clinical incidence of T2D in inflammatory, mitochondrial, metabolic myopathies, and muscular dystrophies and further discussed the molecular basis of these skeletal muscle disorders leading to T2D.

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引用次数: 0

Identification of puberty related miRNAs in the hypothalamus of female mice

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-20 DOI: 10.1016/j.mce.2025.112468

Pavlos Fanis , Maria Morrou , Marios Tomazou , Hend Abdulgadr M. Alghol , George M. Spyrou , Vassos Neocleous , Leonidas A. Phylactou

Background and aims

Puberty is a crucial developmental stage marked by the transition from childhood to adulthood, organized by complex hormonal signaling within the neuroendocrine system. The hypothalamus, a central region in this system, regulates pubertal functions through the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, essential in puberty control, release GnRH in a pulsatile manner, initiating the production of sex hormones. Major influence in pubertal timing has been attributed to genetic predisposition, environmental factors, and nutritional status. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as key regulators in various cellular processes by either repressing genes or activating them by inhibiting their repressors. The present study aims to investigate the involvement of miRNAs in the control of puberty.

Methods

Small RNA sequencing was used to identify and compare the total population of miRNAs in the hypothalamus of female mice before, during and after puberty. Bioinformatic analysis was applied to analyse the expression profile of miRNAs with altered levels followed by pathway enrichment analysis.

Results

Expression levels of several miRNAs were found up- or down-regulated from pre-pubertal to pubertal stage. Furthermore, monitoring the levels of these miRNAs at the post-pubertal stage revealed four expression patterns, in which pathway analysis displayed the associations of these miRNAs with developmental processes, cell cycle regulation, metabolic biosynthesis and epigenetic regulation.

Conclusion

The findings of the present study improve our understanding of the molecular pathways underlying puberty and stress the significance of miRNAs in fine-tuning gene expression within the hypothalamus during this critical developmental stage.

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引用次数: 0

The impact of obesity on mitochondrial dysfunction during pregnancy 肥胖对妊娠期线粒体功能障碍的影响。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-18 DOI: 10.1016/j.mce.2025.112463

Mariana Pacheco de Oliveira, Larissa Espindola da Silva, Bruna Barros Fernandes, Mariella Reinol Steiner, Debora Gehrke Pistóia, Tamires dos Santos Cichella, Luana Bahia Jacinto, Karoline Marcondes Spuldaro, Betine Pinto Moehlecke Iser, Gislaine Tezza Rezin

Mitochondria play a central role in nutrient metabolism, besides being responsible for the production of adenosine triphosphate (ATP), the main source of cellular energy. However, the ATP production process is associated with the generation of reactive oxygen species (ROS), which excessive accumulation can cause mitochondrial dysfunction. This dysfunction, in turn, causes the accumulation of fatty acids in the adipose tissue, triggering a local inflammatory process that can evolve into systemic inflammation. In women with obesity, an increase in lipid levels in the placental environment is observed. The high presence of fatty acids compromises the structural integrity and mitochondrial membrane, culminating in the release of ROS. This process damages the DNA of placental cells and causes an inflammatory state, affecting metabolic efficiency. This vicious cycle is characterized by defects in mitochondrial ATP production, which can lead to lipid accumulation and inflammation. In pregnant women with obesity, these mitochondrial changes play a determining role in pregnancy outcomes. Hence, the objective of this study was to search the literature to review the impact of mitochondrial dysfunction in the maternal obesity.

线粒体除了负责产生三磷酸腺苷（ATP）（细胞能量的主要来源）外，还在营养代谢中起着核心作用。然而，ATP的产生过程与活性氧（ROS）的产生有关，活性氧的过度积累会导致线粒体功能障碍。反过来，这种功能障碍导致脂肪酸在脂肪组织中积累，引发局部炎症过程，进而演变成全身性炎症。在肥胖妇女中，观察到胎盘环境中脂质水平的增加。脂肪酸的大量存在损害了结构完整性和线粒体膜，最终导致ROS的释放。这个过程会破坏胎盘细胞的DNA，导致炎症状态，影响代谢效率。这种恶性循环的特点是线粒体ATP产生缺陷，从而导致脂质积累和炎症。在肥胖孕妇中，这些线粒体变化在妊娠结局中起着决定性作用。因此，本研究的目的是通过文献检索来回顾线粒体功能障碍对产妇肥胖的影响。

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引用次数: 0

GSTA2 overexpression alleviates bis (2-ethylhexyl) phthalate (DEHP)-induced male reproductive disorders by inhibiting oxidative stress-mediated cell apoptosis via the activated PI3K/AKT signaling pathway GSTA2过表达通过激活PI3K/AKT信号通路抑制氧化应激介导的细胞凋亡，减轻邻苯二甲酸二酯（2-乙基己基）（DEHP）诱导的男性生殖障碍。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-17 DOI: 10.1016/j.mce.2025.112462

Lei Wei , Zonggang Feng , Qian Dou , Genhong Mao , Hu Zhao , Xinghua Zhao , Bin Hao

Male reproductive disorders are responsible for approximately 50% of infertility cases. Bis (2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant known for its reproductive toxicity. Oxidative stress is a key mechanism in response to DEHP exposure. Glutathione S-transferase A2 (GSTA2), a member of the glutathione S-transferase family, has the capacity to detoxify environmental toxins. However, its role in regulating DEHP-induced male reproductive disorders remains unexplored. Next, male mice aged 3 weeks were orally administered with DEHP (500 mg/kg/day) for 14 days to induce male reproductive disorders. We observed a decrease in the GSTA2 expression in the testicular tissues of DEHP-treated mice. To investigate the role of GSTA2 in DEHP exposure, lentiviral vectors carrying GSTA2 sequences (1 × 10⁷ TU/mL, 20 μL) were given to mice on the first day of DEHP treatment. GSTA2 overexpression was found to alleviate testicular damage induced by DEHP, as well as to inhibit oxidative stress and subsequent cell apoptosis. In addition, the PI3K/AKT signaling pathway, which is associated with oxidative stress and DEHP exposure, was activated in DEHP-exposed mice following GSTA2 overexpression. Subsequently, mouse spermatocyte GC-2spd cells with DEHP treatment were used to mimic male reproductive disorders in vitro. Consistently, the GSTA2 expression was decreased in GC-2spd cells with DEHP treatment. GSTA2 overexpression inhibited oxidative stress and cell apoptosis in DEHP-treated GC-2spd cells by activating the PI3K/AKT signaling pathway. Moreover, we discovered that GSTA2 overexpression significantly altered the metabolic profiles of DEHP-treated GC-2spd cells. Collectively, our results suggest that GSTA2 overexpression alleviates DEHP-induced male reproductive disorders by suppressing oxidative stress-mediated cell apoptosis via the PI3K/AKT signaling pathway, providing a novel insight into mitigating reproductive toxicity caused by DEHP exposure.

男性生殖障碍导致大约50%的不孕症病例。邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常见的环境污染物，具有生殖毒性。氧化应激是DEHP暴露反应的关键机制。谷胱甘肽s -转移酶A2 （GSTA2）是谷胱甘肽s -转移酶家族的一员，具有解毒环境毒素的能力。然而，其在调节dehp诱导的男性生殖障碍中的作用仍未被探索。然后，给3周龄雄性小鼠口服DEHP （500 mg/kg/天），连续14天诱导雄性生殖障碍。我们观察到dehp处理小鼠睾丸组织中GSTA2表达降低。为了研究GSTA2在DEHP暴露中的作用，在DEHP治疗的第一天，将携带GSTA2序列（1 × 107 TU/mL, 20 μL）的慢病毒载体给予小鼠。GSTA2过表达可减轻DEHP引起的睾丸损伤，并抑制氧化应激和随后的细胞凋亡。此外，GSTA2过表达后，与氧化应激和DEHP暴露相关的PI3K/AKT信号通路在DEHP暴露小鼠中被激活。随后，使用DEHP处理的小鼠精细胞GC-2spd细胞在体外模拟男性生殖障碍。DEHP处理后，GC-2spd细胞中GSTA2表达下降。GSTA2过表达通过激活PI3K/AKT信号通路抑制dehp处理的GC-2spd细胞的氧化应激和细胞凋亡。此外，我们发现GSTA2过表达显著改变了dehp处理的GC-2spd细胞的代谢谱。总之，我们的研究结果表明，GSTA2过表达通过PI3K/AKT信号通路抑制氧化应激介导的细胞凋亡，从而减轻DEHP诱导的男性生殖障碍，为减轻DEHP暴露引起的生殖毒性提供了新的见解。

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引用次数: 0

GDF15 inhibits early-stage adipocyte differentiation by enhancing HOP2 expression and suppressing C/EBPα expression GDF15通过增强HOP2表达和抑制C/EBPα表达抑制早期脂肪细胞分化。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-13 DOI: 10.1016/j.mce.2025.112461

Haeng Jun Kim , Sung-Un Kang , Hyo Jeong Kim , Yun Sang Lee , Chul-Ho Kim

Excessive adipocyte differentiation and accumulation contribute to the development of metabolic disorders. Growth differentiation factor 15 (GDF15) plays an essential role in energy homeostasis and is considered an anti-obesity factor; however, elevated serum levels of endogenous GDF15 have been reported in certain individuals with obesity. In this study, to gain a better understanding of this complex relationship between GDF15 levels and obesity, we investigated GDF15 expression and function during adipogenesis. Compared with mice fed a normal diet, those fed a short-term high-fat diet exhibited a reduction in epididymal white adipose tissue and serum GDF15 expression. These results were confirmed in human adipose-derived stem cells that showed reduced GDF15 expression during adipogenesis differentiation. During adipogenesis, GDF15 was primarily degraded via the autophagy lysosomal pathway, and GDF15 overexpression in pre-adipocytes inhibited adipogenesis by suppressing CCAAT enhancer binding protein alpha (C/EBPα). Furthermore, whereas we detected a reduction in homologous-pairing protein 2 (HOP2) expression during adipogenesis, expression increased in response to an overexpression of GDF15. Furthermore, following knockdown of HOP2 during GDF15 overexpression, there was no suppression of C/EBPα expression. These findings indicate that GDF15 undergoes lysosomal degradation via an autophagic pathway and suppresses adipocyte differentiation via the HOP2-mediated inhibition of C/EBPα expression. Collectively, our findings indicate that GDF15 could serve as a potential therapeutic target for the treatment of metabolic disorders.

脂肪细胞的过度分化和积累有助于代谢紊乱的发展。生长分化因子15 （GDF15）在能量稳态中起重要作用，被认为是抗肥胖因子；然而，据报道，在某些肥胖患者中，血清内源性GDF15水平升高。在本研究中，为了更好地理解GDF15水平与肥胖之间的复杂关系，我们研究了GDF15在脂肪形成过程中的表达和功能。与正常饮食的小鼠相比，短期高脂肪饮食的小鼠附睾白色脂肪组织和血清GDF15表达减少。这些结果在人类脂肪来源的干细胞中得到证实，这些干细胞在脂肪形成分化过程中显示GDF15表达减少。在脂肪形成过程中，GDF15主要通过自噬溶酶体途径降解，并且GDF15在脂肪前细胞中的过表达通过抑制CCAAT增强子结合蛋白α (C/EBPα)来抑制脂肪形成。此外，尽管我们检测到同源配对蛋白2 （HOP2）在脂肪形成过程中的表达减少，但GDF15过表达后表达增加。此外，在GDF15过表达期间，HOP2被敲除后，C/EBPα的表达没有受到抑制。这些发现表明，GDF15通过自噬途径经历溶酶体降解，并通过hop2介导的C/EBPα表达抑制脂肪细胞分化。总之，我们的研究结果表明GDF15可以作为治疗代谢紊乱的潜在治疗靶点。

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引用次数: 0

Transcriptomic analysis of effects of developmental PCB exposure in the hypothalamus of female rats 雌性大鼠下丘脑发育暴露多氯联苯影响的转录组学分析。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-09 DOI: 10.1016/j.mce.2025.112460

Madeline Streifer , Emily N. Hilz , Raj Raval , Dennis C. Wylie , Andrea C. Gore

This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8–18 and after birth from postnatal (P) days 1–21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these latter phenotypes. We used 3’ targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.

本研究调查了雌性大鼠围产期暴露于 Aroclor 1221（A1221）的后果，A1221 是一种弱雌激素多氯联苯（PCB）混合物，也是已知的干扰内分泌的化学物质（EDC）。之前的研究显示了 A1221 对行为和生理的影响，目前的研究将这项工作扩展到对两个参与生殖控制的下丘脑区域进行全面的转录组分析：弓状核（ARC）和前腹腔周围核（AVPV）。雌性 Sprague-Dawley 大鼠在妊娠期间的第 8-18 天和出生后的第 1-21 天喂食经小剂量 A1221（1 毫克/千克）或载体（3% DMSO 麻油）处理的饼干，通过胎盘和哺乳转移接触后代。A1221 对雌性后代的发育、生理和激素影响相对较小。然而，由于之前的研究表明这种暴露与神经行为紊乱有关，我们试图确定大脑转录组的发育编程是否是这些表型的基础。我们在实验雌鼠的下丘脑（弓状核、室管膜前腹侧核）中使用了 3' 靶向 RNA 测序，结果发现基因表达和基因本体（GO）术语以年龄和组织特异性的方式发生了显著变化。最值得注意的是，与突触信号转导、神经递质调节、免疫反应和细胞结构有关的术语被确定了出来。与突触功能和细胞新陈代谢相关的通路的变化也被进一步确定，这表明即使没有明显的发育变化，A1221 暴露也会在分子水平上影响神经发育和神经内分泌过程。这些分子重编程的发现可以解释A1221对行为的影响，并突出了新的分子靶点和途径，值得进一步研究，以了解EDCs对发育中大脑的影响。

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引用次数: 0

EDNRB negatively regulates glycolysis to exhibit anti-tumor functions in prostate cancer by cGMP/PKG pathway EDNRB通过cGMP/PKG通路负调控糖酵解在前列腺癌中发挥抗肿瘤作用。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-07 DOI: 10.1016/j.mce.2025.112459

Xun Li, Bide Liu, Shuheng Wang, Qiang Dong, Jiuzhi Li

Prostate cancer (PCa) is the most prevalent cancer in men and the leading cause of cancer-related mortality. Recent studies have highlighted the pivotal role of glycolysis in tumor progression. This study aimed to investigate the involvement of the EDNRB gene and its ligand endothelin 3 (EDN3) in glycolysis in PCa and to elucidate its underlying molecular mechanism. Quantitative reverse transcription PCR (RT-qPCR) and methylation-specific PCR (MSP) were used to probe EDNRB expression and methylation in PCa tissues. Cell proliferation and glycolysis in PCa cells were evaluated using Cell Counting Kit-8 (CCK-8), EDU staining, Seahorse assay, and biochemical kits to analyze the effects of EDN3/EDNRB. The underlying molecular mechanism was further explored through Western blotting. The in vivo effect of EDNRB on tumor growth was examined using a xenograft tumor model. Our findings revealed that EDNRB was hypermethylated and downregulated in PCa tissues and cell lines. Overexpression of EDNRB or EDN3 led to reduced cell proliferation and downregulation of glycolytic markers. EDNRB also decreased the extracellular acidification rate (ECAR) baseline and increased the oxygen consumption rate (OCR) baseline, indicating a shift away from glycolysis. Additionally, the anticancer effects of EDNRB or EDN3 was reversed upon inhibition of the cGMP/PKG pathway. In vivo, enhanced EDNRB expression significantly suppressed tumor growth. Therefore, EDNRB or EDN3 possess anticancer potential in PCa, primarily through the regulation of glycolysis via the cGMP/PKG pathway.

前列腺癌（PCa）是男性中最常见的癌症，也是癌症相关死亡率的主要原因。最近的研究强调了糖酵解在肿瘤进展中的关键作用。本研究旨在探讨EDNRB基因及其配体内皮素3 （EDN3）在PCa糖酵解中的作用，并阐明其潜在的分子机制。采用定量反转录PCR （RT-qPCR）和甲基化特异性PCR （MSP）检测EDNRB在PCa组织中的表达和甲基化。采用细胞计数试剂盒-8 （CCK-8）、EDU染色、海马法和生化试剂盒分析EDN3/EDNRB对PCa细胞的增殖和糖酵解作用。通过Western blotting进一步探讨其潜在的分子机制。采用异种移植肿瘤模型检测EDNRB对肿瘤生长的体内影响。我们的研究结果显示，EDNRB在PCa组织和细胞系中高甲基化和下调。EDNRB或EDN3过表达导致细胞增殖减少和糖酵解标志物下调。EDNRB还降低了细胞外酸化率（ECAR）基线，增加了耗氧率（OCR）基线，表明糖酵解的转变。此外，EDNRB或EDN3的抗癌作用在抑制cGMP/PKG途径后被逆转。在体内，EDNRB表达增强可显著抑制肿瘤生长。因此，EDNRB或EDN3在PCa中具有抗癌潜力，主要通过cGMP/PKG途径调节糖酵解。

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引用次数: 0