Biochemical and biophysical research communications最新文献

{"title":"DCAF8L1 induces branching morphogenesis and hollow acinar structures remodeling of MCF10A cells in 3D culture by upregulating DDR1","authors":"Fei Liu ,&nbsp;Zhifa Zheng ,&nbsp;Ze Wei ,&nbsp;Lijin Liu ,&nbsp;Su Liu ,&nbsp;Huitian Han ,&nbsp;Annan Liang ,&nbsp;Xuemeng Mu ,&nbsp;Wei Zou ,&nbsp;Wenjing Ma ,&nbsp;Hao Fan ,&nbsp;Changfa Huang ,&nbsp;Jing Hao ,&nbsp;Guangxi Gao ,&nbsp;Lina Zhao ,&nbsp;Zhihong Wu","doi":"10.1016/j.bbrc.2025.151713","DOIUrl":"10.1016/j.bbrc.2025.151713","url":null,"abstract":"<div><div>Mammary morphogenesis is a highly coordinated process involving cellular differentiation, proliferation, and organization to form a bilayered epithelial network of ducts and lobules within the stromal matrix. Here, we identified the DDB1 and CUL4 associated factor 8-like 1(DCAF8L1) as a novel regulator of mammary morphogenesis. To investigate its role, we established stable DCAF8L1-expressing MCF10A cell lines, which normally lack DCAF8L1 expression. Overexpression of DCAF8L1 enhanced cell proliferation, migration, and induced branching morphogenesis and vacuolar structure assembly in three-dimensional (3D) culture. Subsequently, transcriptomic and proteomic analyses identified the discoidin domain receptor tyrosine kinase 1 (DDR1) as a key downstream effector of DCAF8L1. Further investigation revealed that DCAF8L1 upregulates DDR1, leading to activation of the Notch signaling pathway. These findings suggest that DCAF8L1 drives mammary branching morphogenesis and vacuolar structure assembly via DDR1-mediated Notch activation in 3D-cultured MCF10A cells.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151713"},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of early-life stress on LINE-1 in animal model of child neglect","authors":"Masaharu Okano,&nbsp;Ayano Ogata,&nbsp;Hirofumi Aboshi,&nbsp;Masahiro Kondo","doi":"10.1016/j.bbrc.2025.151787","DOIUrl":"10.1016/j.bbrc.2025.151787","url":null,"abstract":"<div><div>The need for objective methods to assess child neglect has intensified. However, no biological indicators have been established for this purpose. Recently, early-life environments such as maternal attachment have been shown to affect the activity of long-interspersed nuclear element-1 (LINE-1, L1) in human infants and mouse pups. Herein, we hypothesized that the L1 copy number may correlate with the duration of neglect stress. To test this hypothesis, we employed a well-established mouse model of maternal separation that simulates early-life neglect. C57BL6/J mouse pups were subjected to daily maternal separation for either three or 6 h for two weeks from postnatal day (PND) one. We minimized the potential confounding effects of variations in maternal care by designating half of the littermates as untreated controls. L1 copy number in DNA extracted from the hippocampus and amygdala tissues at PND15 was quantified using real-time PCR with two different genes (<em>5s-rRNA</em> and <em>Pthlh</em>) as references. The results showed significantly higher L1 copy numbers in the hippocampus of pups separated for 6 h than in untreated controls. In addition, maternal separation duration was found to be correlated with L1 copy number in the hippocampus (<em>r</em> = 0.46, <em>p</em> &lt; 0.001). Furthermore, the amplification of L1 in the hippocampus induced by 6 h of maternal separation was sustained until PND60. This study introduced a novel approach to understanding neglect-related L1 activity and highlighted the potential of L1 elements as an indicator in forensic medicine.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151787"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of JPX in regulating FUS/SLC7A11 signaling pathway mediated ferroptosis in keloid fibroblasts and its potential in scar repair","authors":"Jianhui Tang,&nbsp;Zhaoming Huang,&nbsp;Panpan Yu","doi":"10.1016/j.bbrc.2025.151770","DOIUrl":"10.1016/j.bbrc.2025.151770","url":null,"abstract":"<div><h3>Background</h3><div>Keloid scar, a fibrotic disease initiated by aberrant fibroblast proliferation, is influenced by ferroptosis. This investigation aims to elucidate the mechanism of lncRNA JPX regulating ferroptosis in keloid fibroblasts.</div></div><div><h3>Methods and results</h3><div>We procured 30 samples of keloid tissue and adjacent normal skin tissues from patients undergoing treatment for keloid scars, subsequently isolating fibroblasts from both the keloid lesions and unaffected portions. JPX expression levels in these lesion and keloid fibroblast samples were detected using qRT-PCR. We then validated the regulatory role of JPX on FUS and SLC7A11 through RNA immunoprecipitation and actinomycin D assays. Subsequently, we overexpressed or silenced JPX and/or SLC7A11 in keloid fibroblasts under conditions with or without ferroptosis inhibitor Fer-1, assessing cell viability, migration, invasion, extracellular matrix (ECM) markers via MTT, Transwell and Western blot assays, and evaluating cellular iron content, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) levels as well as the expression of ferroptosis-related proteins to assess ferroptosis. JPX was up-regulated in keloid tissue and keloid fibroblasts. JPX promoted SLC7A11 stability and expression through FUS. JPX silence suppressed viability, migration, invasion and ECM production, yet facilitated ferroptosis of keloid fibroblasts, while these effects could be reversed by Fer-1 or SLC7A11 overexpression.</div></div><div><h3>Conclusion</h3><div>JPX regulates ferroptosis within fibroblast derived from scar tissue via the FUS/SLC7A11 pathway, demonstrating its potential utility in facilitating scar repair processes.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151770"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic ablation and regeneration of arterial valve in zebrafish","authors":"Zongyi Duan,&nbsp;Hao Cao,&nbsp;Mengting Xu,&nbsp;Wenping Huang,&nbsp;Yuanhui Peng,&nbsp;Zhenya Shen,&nbsp;Shijun Hu,&nbsp;Yanchao Han","doi":"10.1016/j.bbrc.2025.151786","DOIUrl":"10.1016/j.bbrc.2025.151786","url":null,"abstract":"<div><div>Aortic valve diseases are prevalent and severe cardiovascular conditions with limited treatment options beyond surgical intervention. The ability to regenerate aortic valves would revolutionize the management of these diseases. Utilizing the zebrafish model, which possesses remarkable regenerative capacities, we developed a chemogenetic arterial valve ablation model using a zebrafish-codon optimized nitroreductase. We found that arterial valve ablation led to blood regurgitation and impaired cardiac function, which are commonly associated with aortic valve diseases. Following ablation, zebrafish arterial valve could fully regenerate and restore valvular and cardiac function. Moreover, suppression of blood flow significantly impedes valve regeneration, indicating the importance of hemodynamic forces in this process. Our research has successfully established a robust aortic valve injury model to study the cellular and molecular mechanisms underlying its regeneration process which will facilitate the development of innovative therapeutic strategies tailored for aortic valve diseases.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151786"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of biochemical and biophysical properties, molecular docking and dynamics studies on azelastine","authors":"Natarajan Elangovan ,&nbsp;Natarajan Arumugam ,&nbsp;Anandaraj Pennamuthiriyan ,&nbsp;Anuj Garg ,&nbsp;Venketesh Sivaramakrishnan ,&nbsp;Subbarao Kanchi ,&nbsp;Madhappan Santhamoorthy","doi":"10.1016/j.bbrc.2025.151781","DOIUrl":"10.1016/j.bbrc.2025.151781","url":null,"abstract":"<div><div>The structure of the 4-(4-chlorobenzyl)-2-(1-methylazepan-4-yl) phthalazin-1(2H)-one (IA) was optimized through computational study. The optimized structure revealed that the bond length between atoms C3 and C5 was the longest at 1.54 Å, while the bond between atoms C10 and H31 had the lowest length at about 1.01 Å, respectively. The natural bond orbital (NBO) analysis indicates that the bonding π(C3–C20) to anti-bonding π∗(N2–C3) interaction exhibits the most significant stabilization energy of about 253.59 kcal/mol. Due to the solvent's influence, the gas phase MEP value and HOMO-LUMO band gap value are lower, when compared to solvents. A localized bond pair that undergoes movement between two atoms, and a bond pair that undergoes movement between two different pairs of atoms are identified by electron localized function (ELF), localized orbital locator (LOL), and average localized ionization energy (ALIE) studies, respectively. The electron density and thermodynamic properties were determined using Gaussian software. This study examined various parameters such as non-linear optical (NLO), molecular electrostatic potential (MEP), UV–vis, and HOMO-LUMO in different solvents. Further, the biological activity of the IA compound was studied using molecular docking and dynamics on the target Mycobacterium tuberculosis ArgF (7NOR) protein, which showed favorable protein-ligand interaction energy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151781"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravesical chemotherapy enhances anti-tumor immunity in bladder cancer by modulating CD8+ T cell activation and Treg populations","authors":"Rui Chen ,&nbsp;Shuangfeng Ding ,&nbsp;Xiaocong Fu ,&nbsp;Gang Liu","doi":"10.1016/j.bbrc.2025.151782","DOIUrl":"10.1016/j.bbrc.2025.151782","url":null,"abstract":"<div><div>Bladder cancer is one of the most common malignancies of the urinary system, with standard treatments including surgery, radiotherapy, and chemotherapy. However, these conventional approaches often yield suboptimal outcomes, necessitating exploring alternative therapeutic strategies. This study evaluated the efficacy of intravesical chemotherapy, both alone and in combination with immunotherapy, using an orthotopic mouse model of bladder cancer.</div><div>To establish the model, luciferase-expressing bladder cancer cells were orthotopically implanted into immunocompetent mice. Treatment efficacy was assessed by monitoring changes in bioluminescence imaging (BLI) signal intensity, indicative of tumor burden, and by measuring tumor weights post-mortem. Mice were divided into four groups: G1: untreated control; G2: intravesical chemotherapy with 40 mph Doxorubicin (0.05 ml per mouse, bladder instillation); G3intraperitoneal (i.p.) chemotherapy with 10 mph Doxorubicin; G4: immune combination therapy with 10 mph Doxorubicin (i.p.) plus 10 mph PD-L1 inhibitor (i.p.).</div><div>Results demonstrated that intravesical chemotherapy significantly reduced tumor burden compared to both conventional systemic chemotherapy and immune combination therapy (p-value &lt;0.05). Flow cytometry analysis revealed a notable decrease in CD8⁺ T cell expression in both the intravesical and conventional chemotherapy groups (<em>p</em> value &lt; 0.01). Additionally, Treg cell expression was moderately reduced in the conventional and immune combination therapy groups (<em>p</em> value &lt; 0.05). Notably, intravesical chemotherapy led to a significant increase in CD69 activation on CD8⁺ T cells (<em>p</em> value &lt; 0.05), suggesting enhanced T cell activation, while also moderately reducing PD-1 expression, a marker of T cell exhaustion (<em>p</em> value &lt; 0.05).Histological analysis, including hematoxylin and eosin (HE) staining and Ki-67 immunohistochemistry, further confirmed significant differences in tumor morphology and proliferation among the treatment groups (<em>p</em> value &lt; 0.05). These findings suggest that intravesical chemotherapy not only exerts a direct anti-tumor effect but also modulates the immune response by activating CD8⁺ T cells and mitigating T cell exhaustion.</div><div>To conclusion, this study highlights the potential of intravesical chemotherapy as a promising and clinically feasible approach for bladder cancer treatment, warranting further investigation in translational and clinical practice.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"764 ","pages":"Article 151782"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myricetin promotes migration and prevents palmitate-induced apoptosis in cultured tenocytes through AMPK-dependent pathways","authors":"Do Su Lim ,&nbsp;Sung Ho Ahn ,&nbsp;Wonjun Cho ,&nbsp;Hyeon Ji Gwon ,&nbsp;Jun Hwi Ko ,&nbsp;Min Kyung Pyo ,&nbsp;A.M. Abd El-Aty ,&nbsp;Emced Elubeyd ,&nbsp;Jong Wook Shin ,&nbsp;Ji Hoon Jeong ,&nbsp;Kyoung-Tae Lee ,&nbsp;Tae Woo Jung","doi":"10.1016/j.bbrc.2025.151764","DOIUrl":"10.1016/j.bbrc.2025.151764","url":null,"abstract":"<div><div>Myricetin (Myr), a flavonoid present in vegetables and fruits, has been shown to ameliorate inflammation and oxidative stress in various disease models. However, the effects of Myr on hyperlipidemic tenocytes have not been studied. Herein, we aimed to investigate the effects of Myr on the features of tendinopathy in cultured tenocytes under hyperlipidemic conditions. Reactive oxygen species (ROS) were detected by DCFDA. Hydrogen peroxide (H₂O₂), malondialdehyde (MDA), and caspase 3 activity were quantified <em>via</em> matched assay kits. Apoptotic cells were detected <em>via</em> TUNEL staining. Proteins investigated in this study were evaluated through Western blotting. Treatment with Myr enhanced tenocyte migration and prevented apoptosis, inflammation and oxidative stress in palmitate-treated tenocytes. Myr treatment increased the phosphorylation of AMPK, and the expression of PGC1α and FGF2. siRNA targeting AMPK abrogated the effects of Myr on palmitate-treated tenocytes. However, FGF2 siRNA reduced the impacts of Myr on only cell migration and ECM signaling. These <em>in vitro</em> results suggest that Myr promotes tenocyte migration and ECM signaling <em>via</em> AMPK/FGF2 signaling and attenuates apoptosis through the AMPK-mediated suppression of inflammation and oxidative stress in hyperlipidemic tenocytes. This study sheds light on therapeutic strategies for treating obesity-related tendinopathy.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151764"},"PeriodicalIF":2.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFBP1 promotes triple-negative breast cancer progression through the KLK10-AKT axis","authors":"Ziqi wang ,&nbsp;Ruoqing Hou ,&nbsp;Shiyu Wang ,&nbsp;Min Chen ,&nbsp;Dongdong Zheng ,&nbsp;Zhiming Zhang ,&nbsp;Lu Bai ,&nbsp;Cai Chang ,&nbsp;Shichong Zhou","doi":"10.1016/j.bbrc.2025.151763","DOIUrl":"10.1016/j.bbrc.2025.151763","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is highly malignant, with rapid tumor growth and metastasis. Due to ER-, PR- and HER2-of TNBC, FGFR pathway play a pivotal role in the progression of TNBC. Its ligand FGFs is mostly released from the extracellular matrix by fibroblast growth factor binding protein 1 (FGFBP1). However, little is known about the role of FGFBP1 in TNBC. In this study, we found that overexpression of FGFBP1 significantly promoted the proliferation, migration and invasion of TNBC cells in vitro and in vivo and vice versa. Mechanistically, overexpression of FGFBP1 upregulated the expression of KLK10, thereby activating AKT, which led to proliferation, migration and invasion of TNBC cells. After knocking down FGFBP1, the expression of KLK10 was reduced and the AKT pathway was inhibited. In addition, knocking down KLK10 or inhibiting AKT pathway impaired the promotion effect of overexpression of FGFBP1 on the proliferation and invasion of TNBC cells. These results suggest that FGFBP1 may promote the proliferation, migration and invasion of TNBC cells through the KLK10-AKT axis. Targeting FGFBP1 may serve as a new therapeutic strategy for TNBC.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151763"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics and experimental verification to dissect the mechanisms and bioactive ingredients of Radix Rehmanniae in treating multiple sclerosis","authors":"Jing Xie ,&nbsp;Meiling Wu ,&nbsp;Li Li ,&nbsp;Lixia Zhu ,&nbsp;Liang Hu ,&nbsp;Yuzhen Li ,&nbsp;Wenting Li","doi":"10.1016/j.bbrc.2025.151790","DOIUrl":"10.1016/j.bbrc.2025.151790","url":null,"abstract":"<div><div>Multiple sclerosis (MS), as a primary cause of nontraumatic disability in young adults, has no effective treatment yet. <em>Radix Rehmanniae</em> (RR), a typical Traditional Chinese Medicine (TCM), is commonly used in MS patients as a most frequent herbal item in TCM formulas. Our recent study demonstrated that RR alleviated neurological deficits in an experimental MS model. However, direct evidence regarding the holistic mechanisms and bioactive components of RR for MS remains unclear. In this study, we employed an integrative strategy combining bioinformatics and experimental validation to profile the holistic mechanisms of RR, identify its bioactive components, and investigate their potential targets in MS. First, a network pharmacology approach was used to construct a “compound-target-pathway” network, indicating the action of RR on MS in a multicomponent-multitarget mode, and predicting Echinacoside and Acteoside as the primary bioactive ingredients. Bioinformatics analyses of transcriptomics and single-cell RNA sequencing based on GSE datasets indicated that oxidative stress and inflammatory/immune regulation in microglia might serve as crucial mechanisms of Echinacoside and Acteoside in MS pathology. Then, <em>in vitro</em> assays validated that Echinacoside and Acteoside possessed anti-inflammatory and antioxidant properties by scavenging ONOO⁻ and H₂O₂ directly, and suppressing microglia-derived ONOO⁻ production through inhibition of NF-κB-mediated iNOS and NADPH oxidase. In addition, molecular docking showed strong affinities between Acteoside and inflammation-related targets TGF-β and SMAD2. These findings provide the scientific evidence for clinical application of RR and bring novel insights into MS drug development.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"763 ","pages":"Article 151790"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A CRISPR-based high-throughput screening system identifies bromodomain inhibitors as transcriptional suppressors of CYP11B1","authors":"Ryo Ito,&nbsp;Taichi Nakano,&nbsp;Akira Sugawara,&nbsp;Atsushi Yokoyama","doi":"10.1016/j.bbrc.2025.151779","DOIUrl":"10.1016/j.bbrc.2025.151779","url":null,"abstract":"<div><div><em>CYP11B1</em> encodes steroid 11β-hydroxylase, the final rate-limiting enzyme for cortisol biosynthesis in the adrenal cortex. Excessive cortisol production is a hallmark of Cushing's disease (CD). While direct enzymatic inhibitors have been explored, achieving specificity remains a challenge due to the high homology between <em>CYP11B1</em> and <em>CYP11B2</em>, highlighting transcriptional suppression of <em>CYP11B1</em> as an alternative therapeutic strategy. To identify transcriptional regulators of <em>CYP11B1</em>, we generated genome-edited H295R adrenal cells carrying a luciferase reporter knocked into the endogenous <em>CYP11B1</em> locus. Using this reporter cell line, we established a high-throughput screening (HTS) platform and screened a focused chemical library targeting epigenetic-related factors, given the importance of epigenetic mechanisms in gene regulation. Among eight candidate compounds identified, we focused on JQ1, a bromodomain inhibitor. JQ1 significantly suppressed Forskolin-induced <em>CYP11B1</em> promoter activity and mRNA expression without causing cytotoxicity, suggesting the involvement of epigenetic readers in the transcriptional regulation of steroidogenic genes. Furthermore, the reporter-based HTS platform developed here, when combined with our previously established <em>CYP11B2</em>-luciferase system, may facilitate the identification of compounds that selectively modulate adrenal steroidogenic pathways. These findings provide a foundation for the development of novel transcription-targeted therapies for CD.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"762 ","pages":"Article 151779"},"PeriodicalIF":2.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}