Molecular and Cellular Endocrinology最新文献

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

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub Date: 2025-01-07 DOI: 10.1016/j.mce.2025.112459

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

{"title":"EDNRB negatively regulates glycolysis to exhibit anti-tumor functions in prostate cancer by cGMP/PKG pathway.","authors":"Xun Li, Bide Liu, Shuheng Wang, Qiang Dong, Jiuzhi Li","doi":"10.1016/j.mce.2025.112459","DOIUrl":"10.1016/j.mce.2025.112459","url":null,"abstract":"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.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112459"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub 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

{"title":"The impact of obesity on mitochondrial dysfunction during pregnancy.","authors":"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","doi":"10.1016/j.mce.2025.112463","DOIUrl":"10.1016/j.mce.2025.112463","url":null,"abstract":"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.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112463"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A guide to pathophysiology, signaling pathways, and preclinical models of liver fibrosis. 肝纤维化的病理生理学、信号通路和临床前模型指南。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub Date: 2025-01-02 DOI: 10.1016/j.mce.2024.112448

Mehonaz Sultana, Md Asrarul Islam, Rhema Khairnar, Sunil Kumar

{"title":"A guide to pathophysiology, signaling pathways, and preclinical models of liver fibrosis.","authors":"Mehonaz Sultana, Md Asrarul Islam, Rhema Khairnar, Sunil Kumar","doi":"10.1016/j.mce.2024.112448","DOIUrl":"10.1016/j.mce.2024.112448","url":null,"abstract":"Liver fibrosis is potentially a reversible form of liver disease that evolved from the early stage of liver scarring as a consequence of chronic liver injuries. Recurrent injuries in the liver without any appropriate medication cause the injuries to get intense and deeper, which gradually leads to the progression of irreversible cirrhosis or carcinoma. Unfortunately, there are no approved treatment strategies for reversing hepatic fibrosis, making it one of the significant risk factors for developing advanced liver disorders and liver disease-associated mortality. Consequently, the interpretation of the fundamental mechanisms, etiology, and pathogenesis is crucial for identifying the potential therapeutic target as well as evaluating novel anti-fibrotic therapy. However, despite innumerable research, the functional mechanism and disease characteristics are still obscure. To accelerate the understanding of underlying disease pathophysiology, molecular pathways and disease progression mechanism, it is crucial to mimic human liver disease through the formation of precise disease models. Although various in vitro and in vivo liver fibrotic models have emerged and developed already, a perfect clinical model replicating human liver diseases is yet to be established, which is one of the major challenges in discovering proper therapeutics. This review paper will shed light on pathophysiology, signaling pathways, preclinical models of liver fibrosis, and their limitations.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112448"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endocrine-disrupting chemical, methylparaben, in environmentally relevant exposure promotes hazardous effects on the hypothalamus-pituitary-thyroid axis. 内分泌干扰化学物质，对羟基苯甲酸甲酯，在环境相关的暴露促进对下丘脑-垂体-甲状腺轴的有害影响。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub Date: 2024-12-24 DOI: 10.1016/j.mce.2024.112444

Damáris Barcelos Cunha Azeredo, Denilson de Sousa Anselmo, Ana Clara Falcão Veríssimo, Luana Lopes de Souza, Patricia Cristina Lisboa, Paula Soares, Ana Paula Santos-Silva, Jones Bernardes Graceli, Denise Pires de Carvalho, D'Angelo Magliano, Leandro Miranda-Alves

{"title":"Endocrine-disrupting chemical, methylparaben, in environmentally relevant exposure promotes hazardous effects on the hypothalamus-pituitary-thyroid axis.","authors":"Damáris Barcelos Cunha Azeredo, Denilson de Sousa Anselmo, Ana Clara Falcão Veríssimo, Luana Lopes de Souza, Patricia Cristina Lisboa, Paula Soares, Ana Paula Santos-Silva, Jones Bernardes Graceli, Denise Pires de Carvalho, D'Angelo Magliano, Leandro Miranda-Alves","doi":"10.1016/j.mce.2024.112444","DOIUrl":"10.1016/j.mce.2024.112444","url":null,"abstract":"Methylparaben (MP) belongs to the paraben class and is widely used as a preservative in personal care products, medicines, and some foods. MP acts as an endocrine disrupting chemical (EDC) on the hypothalamic-pituitary-thyroid (HPT) axis. However, the effects of MP have not yet been completely elucidated, as published results are scarce and controversial. The objective of this work was to evaluate the effects of subacute exposure to MP on the HPT axis of male rats. To achieve this, in this study the animals were divided into four experimental groups: control, MP3, MP30 and MP300 (3, 30 and 300 μg/kg/day, respectively). The rats were gavage for 14 days and sacrificed at the end of MP treatment. Our findings demonstrated that MP can promote important changes in thyroid morphology, including a decrease in follicular area, colloid area, epithelial area, and epithelial height, affecting the homeostasis of the HPT axis, and affecting the expression of genes related to hormonal biosynthesis. Furthermore, changes in interstitial collagen deposition were also demonstrated. Finally, we conclude that exposure to MP can be harmful to health, as it is involved in the dysregulation of the thyroid gland, affecting its morphophysiology, suggesting that even doses considered safe by current legislation can be dangerous and should be reconsidered.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112444"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Housing temperature influences metabolic phenotype of heart failure with preserved ejection fraction in J vs N strain C57BL/6 mice. 房舍温度对jvs N型C57BL/6小鼠保留射血分数心力衰竭代谢表型的影响

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub Date: 2025-01-07 DOI: 10.1016/j.mce.2025.112457

Rajesh Chaudhary, Tahra K Suhan, Chao Wu, Afnan Alzamrooni, Nageswara Madamanchi, Ahmed Abdel-Latif

{"title":"Housing temperature influences metabolic phenotype of heart failure with preserved ejection fraction in J vs N strain C57BL/6 mice.","authors":"Rajesh Chaudhary, Tahra K Suhan, Chao Wu, Afnan Alzamrooni, Nageswara Madamanchi, Ahmed Abdel-Latif","doi":"10.1016/j.mce.2025.112457","DOIUrl":"10.1016/j.mce.2025.112457","url":null,"abstract":"Preclinical heart failure studies rely heavily on mouse models despite their higher metabolic and heart rates compared to humans. This study examines how mouse strain (C57BL/6J vs. C57BL/6N) and housing temperature (23 °C vs. 30 °C) affect a well-established two-hit HFpEF model using high-fat diet with L-NAME treatment in male C57BL/6 mouse. Metabolic parameters and cardiac function were assessed at baseline, week 5, and week 15. Thermoneutral housing (30 °C) reduced early diastolic dysfunction in the J strain and altered metabolic profiles in both strains, decreasing energy expenditure and fat oxidation. The J strain specifically showed reduced respiratory exchange ratio and glucose oxidation at 30 °C. While physical activity remained constant across groups, both strains exhibited increased cardiac fibrosis and inflammatory gene expression under HFD + L-NAME, independent of housing temperature. These findings reveal strain-specific physiological adaptations to housing temperature, emphasizing the need to consider environmental conditions in heart failure research carefully.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112457"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub 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

{"title":"GDF15 inhibits early-stage adipocyte differentiation by enhancing HOP2 expression and suppressing C/EBPα expression.","authors":"Haeng Jun Kim, Sung-Un Kang, Hyo Jeong Kim, Yun Sang Lee, Chul-Ho Kim","doi":"10.1016/j.mce.2025.112461","DOIUrl":"10.1016/j.mce.2025.112461","url":null,"abstract":"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.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"598 ","pages":"112461"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of puberty related miRNAs in the hypothalamus of female mice.

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub 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

{"title":"Identification of puberty related miRNAs in the hypothalamus of female mice.","authors":"Pavlos Fanis, Maria Morrou, Marios Tomazou, Hend Abdulgadr M Alghol, George M Spyrou, Vassos Neocleous, Leonidas A Phylactou","doi":"10.1016/j.mce.2025.112468","DOIUrl":"10.1016/j.mce.2025.112468","url":null,"abstract":"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.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112468"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional analysis of SRY variants in individuals with 46,XY differences of sex development. 性别发育差异46，xy个体中SRY变异的功能分析

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-03-01 Epub Date: 2025-01-07 DOI: 10.1016/j.mce.2025.112458

Firman P Idris, Jocelyn van den Bergen, Gorjana Robevska, Lucas G A Ferreira, Karen R Ferreira, Marina M L Kizys, Magnus R Dias da Silva, Hennie T Bruggenwirth, Yolande van Bever, Andrew H Sinclair, Katie L Ayers

{"title":"Functional analysis of SRY variants in individuals with 46,XY differences of sex development.","authors":"Firman P Idris, Jocelyn van den Bergen, Gorjana Robevska, Lucas G A Ferreira, Karen R Ferreira, Marina M L Kizys, Magnus R Dias da Silva, Hennie T Bruggenwirth, Yolande van Bever, Andrew H Sinclair, Katie L Ayers","doi":"10.1016/j.mce.2025.112458","DOIUrl":"10.1016/j.mce.2025.112458","url":null,"abstract":"In mammals, male sexual development is initiated by the expression of the Sex-determining-Region-Y (SRY) gene. SRY contains a highly conserved high mobility group (HMG) box essential for DNA binding and activity. Variants in SRY cause Differences of Sex Development (DSD), accounting for 10-15% of 46, XY gonadal dysgenesis cases. Here, we present the functional analysis of five SRY coding variants identified in patients with 46, XY DSD. Four variants (p.Asp58Glu, p.Arg75Lys, p.Met85Thr, and p.Arg86Ter) are located within the HMG box and one variant (p.Tyr198Cysfs∗18) located in the C-terminal domain. We functionally characterise the impact of these variants in vitro, investigating SRY localisation and transactivational activity using SOX9 regulatory elements that are responsive to SRY. We find that three variants (p.Met85Thr, p.Arg86Ter, and p.Tyr198Cysfs∗18) have reduced or abolished transactivational activity suggesting these are pathogenic, with the p.Arg86Ter variant undetectable in our assays and the p.Met85Thr variant exhibiting reduced nuclear localisation. The pathogenic mechanisms underlying reduced activity of the novel elongated p.Tyr198Cysfs∗18 variant is however unclear, although this variant also affected localisation. In contrast, two additional variants (p.Asp58Glu and p.Arg75Lys) had no discernible effects on nuclear localisation or transactivational activity despite in silico analysis predicting impaired DNA binding. Taken together, our data establish the likely pathogenicity of these SRY variants and improve diagnostic certainty for the patients in which they were identified.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112458"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liraglutide promotes osteogenic differentiation of mesenchymal stem cells by inhibiting M1 macrophage polarization and CXCL9 release in vitro. 利拉鲁肽通过体外抑制M1巨噬细胞极化和CXCL9释放促进间充质干细胞成骨分化。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-02-01 Epub Date: 2024-12-18 DOI: 10.1016/j.mce.2024.112441

Yilin He, Wenpeng Song, Yinxin Deng, Xiao Lin, Zhenhua Gao, Pan Ma

{"title":"Liraglutide promotes osteogenic differentiation of mesenchymal stem cells by inhibiting M1 macrophage polarization and CXCL9 release in vitro.","authors":"Yilin He, Wenpeng Song, Yinxin Deng, Xiao Lin, Zhenhua Gao, Pan Ma","doi":"10.1016/j.mce.2024.112441","DOIUrl":"10.1016/j.mce.2024.112441","url":null,"abstract":"As a GLP-1 receptor agonist widely used in treating type 2 diabetes, liraglutide shows potential applications in bone tissue engineering. This study investigated liraglutide's direct effects on rat bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation and its regulatory mechanism through macrophage polarization. Results showed that liraglutide significantly enhanced BMSC migration and osteogenic differentiation. Additionally, liraglutide markedly inhibited M1 macrophage polarization induced by LPS and IFN-γ, reducing inflammatory factors CXCL9 and TNF-α secretion, possibly by partially reversing M1 macrophage regulatory signals (AMPK and NF-κB pathways). Compared to M1 macrophage-conditioned medium (M1-CM), conditioned medium from liraglutide-treated macrophages showed stronger promotion of BMSC osteogenic differentiation, though this effect was reversed by CXCL9 addition. The study demonstrates that liraglutide enhances BMSC osteogenic capacity both directly and by inhibiting M1 macrophage polarization and CXCL9 secretion, offering a new therapeutic option for severe bone defects with inflammatory responses.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112441"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NAT10 drives endometriosis progression through acetylation and stabilization of TGFB1 mRNA. NAT10通过乙酰化和TGFB1 mRNA的稳定驱动子宫内膜异位症的进展。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2025-02-01 Epub Date: 2024-12-26 DOI: 10.1016/j.mce.2024.112447

Na Liu, Jing YangOu, Chenxuan Wei, Guojing Li, Ruoer Yu, Yu Lin, Hong Xu

{"title":"NAT10 drives endometriosis progression through acetylation and stabilization of TGFB1 mRNA.","authors":"Na Liu, Jing YangOu, Chenxuan Wei, Guojing Li, Ruoer Yu, Yu Lin, Hong Xu","doi":"10.1016/j.mce.2024.112447","DOIUrl":"10.1016/j.mce.2024.112447","url":null,"abstract":"Endometriosis, a gynecological disorder marked by pelvic pain and infertility, has its pathogenesis and pathophysiology significantly influenced by epigenetics, as these factors have been well characterized. However, the role of RNA-mediated epigenetic regulation in endometriosis remains to be elucidated. In our study, we found that N4-acetylcytidine (ac4C) RNA modification and N-acetyltransferase 10 (NAT10) were significantly upregulated in endometrial lesions compared to eutopic endometrium. Knockdown of NAT10 suppressed endometrial epithelial cell proliferation, epithelial-to-mesenchymal transition (EMT), and cell cycle processes in vitro. RNA-seq and acRIP-seq analyses revealed that the knockdown of NAT10 impaired cell proliferation and the TGF-beta signaling pathway. We further identified that ac4C RNA modification enhanced TGFB1 mRNA stability and expression levels, and inhibition of NAT10 activity by Remodelin effectively suppressed the growth of ectopic lesions in an endometriosis mouse model. Collectively, our findings reveal that increased NAT10-mediated ac4C modification enhances TGFB1 mRNA stability, thereby promoting the development of endometriosis. This discovery lays the molecular foundation for future therapeutic approaches targeting endometriosis.","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112447"},"PeriodicalIF":3.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0