Cell Biochemistry and Biophysics最新文献

{"title":"IRF7 Activates LCN2 Transcription to Enhance LPS-Induced Acute Lung Injury by Inducing Macrophage Ferroptosis and M1 Polarization.","authors":"Yali Lv, Lefeng Zhang","doi":"10.1007/s12013-024-01651-9","DOIUrl":"10.1007/s12013-024-01651-9","url":null,"abstract":"<p><p>Acute lung injury (ALI), a severe pulmonary disorder that poses a significant threat to life, is closely associated with macrophage ferroptosis and polarization. Lipocalin 2 (LCN2) has been previously reported to be implicated in the pathogenesis of ALI. However, the specific role of LCN2 in macrophage ferroptosis and polarization remains undetermined. Lipopolysaccharide (LPS) was used to establish a mouse model of ALI and also to stimulate mouse RAW264.7 cells. H&E staining was used for histopathologic evaluation, and immunohistochemistry analysis was used to determine the 4-HNE-positive cells. The secretion levels of TNF-α, IL-6, and IL-1β were assessed by ELISA. Gene and protein expression assays were performed using quantitative PCR and immunoblotting. The levels of MDA, GSH, ROS, and lipid ROS were detected to evaluate the alteration in ferroptosis. CD86⁺ and CD206⁺ cells were quantified by flow cytometry. The relationship between LCN2 and interferon regulatory factor 7 (IRF7) was confirmed by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. LCN2 expression was upregulated in the lungs of LPS-induced ALI mice and LPS-stimulated RAW264.7 cells. In LPS-induced ALI mice, the depletion of LCN2 alleviated lung injury and ferroptosis, and also inhibited inflammation and macrophage M1 polarization. In LPS-stimulated RAW264.7 cells, the depletion of LCN2 suppressed ferroptosis, inflammation, and M1 polarization. Mechanistically, IRF7 enhanced LCN2 transcription in RAW264.7 cells by binding to its promoter region. More importantly, the silencing of IRF7 inhibited ferroptosis and M1 polarization in LPS-stimulated RAW264.7 cells by downregulating LCN2. Taken together, the IRF7/LCN2 cascade enhances the ferroptosis and M1 polarization of LPS-stimulated macrophages, thereby exacerbating ALI. Anti-IRF7 and anti-LCN2 therapies might potentially be exploited for the prevention and treatment in ALI.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2415-2430"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Water-Soluble Ginseng Oligosaccharides Prevent Scopolamine-Induced Cholinergic Dysfunction and Inflammatory Cytokine Overexpression.","authors":"Ting Zeng, Chengwei Zhang, Lili Sun, Haiyan Xu","doi":"10.1007/s12013-024-01660-8","DOIUrl":"10.1007/s12013-024-01660-8","url":null,"abstract":"<p><p>Cholinergic deficiency and neuroinflammation are the two main factors of Alzheimer's disease. Recent studies have shown that water-soluble ginseng oligosaccharides (WGOS) derived from Panax ginseng roots can protect against scopolamine-induced impairments in learning and memory. However, the fundamental mechanisms remain unclear for the most part. The purpose of this study was to examine the effect of WGOS on cholinergic function and protein levels of proinflammatory cytokines in the hippocampus of mice. Mice were first pretreated with WGOS or saline, and then treated with scopolamine to establish an Alzheimer's disease model. The cognition memory of the mice was assessed through the behavioral test. The effect of WGOS on the cholinergic system was evaluated by measuring acetylcholine (ACh) neurotransmitter concentration and acetylcholinesterase (AChE) activity in the hippocampus. Using ELISA, the inflammatory cytokines IL-1β and TNF-α in the hippocampus were identified. This study found that WGOS treatment prevented the scopolamine-induced impairment of mice's recognition memory, as seen by their enhanced object recognition. In addition, WGOS prevented the scopolamine-induced decrease in ACh concentration and increase in AChE activity. Moreover, WGOS treatment inhibited scopolamine-induced upregulation of the inflammatory proteins IL-1β and TNF-α. These findings suggest that the amelioration of scopolamine-induced cognitive impairment in mice by WGOS was a consequence of the control of cholinergic function and inflammatory response in the hippocampus. Our findings suggest that WGOS should be investigated as a dietary supplement or medication for the treatment of learning and memory disorders in humans.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2511-2518"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142919025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-145b/AP2B1 Axis Contributes to Noise-induced Sensorineural Hearing Loss In a Male Mouse Model.","authors":"Xiang Gu, Mengxian Jiang, Wei Chen","doi":"10.1007/s12013-024-01665-3","DOIUrl":"10.1007/s12013-024-01665-3","url":null,"abstract":"<p><p>Sensorineural hearing loss (SNHL) is an increasingly prevalent sensory disorder, but the underlying mechanisms remain poorly understood. Adaptor related protein complex 2 subunit beta 1 (AP2B1) has been indicated to be detectable in mature cochleae. Nonetheless, it is unclear whether AP2B1 is implicated in the progression of SNHL. Male CBA/J mice were exposed to 2-20 kHz broadband noise at 96 or 101 dB SPL to induce temporary or permanent threshold shifts (TTS or PTS). Auditory brainstem responses were measured for hearing loss evaluation. Bioinformatics analysis was used to predict the upstream miRNAs of Ap2b1. RT-qPCR and western blotting were utilized to determine miR-145b and AP2B1 expression in mouse cochleae. Luciferase reporter assay was implemented to verify the interaction between Ap2b1 and miR-145b. Bioinformatics analysis identified miR-145b as an upstream miRNA of Ap2b1. AP2B1 expression was decreased and miR-145b expression was increased in mouse cochleae after PTS noise exposure. miR-145b targeted and negatively regulated Ap2b1 in PTS noise-exposed mice. Depletion of miR-145b alleviated auditory threshold shifts and outer hair cell loss in mice with exposure to PTS noise. In conclusion, inhibition of miR-145b ameliorates noise-induced SNHL in mice by upregulating AP2B1 expression.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2567-2575"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAPRIN1 Transcriptionally Activated PLPP4 to Inhibit DOX Sensitivity and Promote Breast Cancer Progression.","authors":"Xiaorong Yuan, Xuejie Yang","doi":"10.1007/s12013-024-01614-0","DOIUrl":"10.1007/s12013-024-01614-0","url":null,"abstract":"<p><strong>Background: </strong>Phospholipid phosphatase 4 (PLPP4) has been identified as a potential regulator of cancer cell dynamics, however, the role of PLPP4 in breast cancer (BC) progression and the sensitivity of BC cells to doxorubicin (DOX) remain elusive.</p><p><strong>Methods: </strong>The study analyzed the expression of PLPP4 and cell cycle-associated protein 1 (CAPRIN1) expression in BC tissues and cells using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting assays. Functional assays including colony formation, EdU, Transwell, and flow cytometry were employed to assess cellular behaviors. The sensitivity of BC cells to DOX was analyzed by CCK-8 assay and an in vivo xenograft model assay. The association between PLPP4 and CAPRIN1 was investigated using RNA immunoprecipitation assay and dual-luciferase reporter assay.</p><p><strong>Results: </strong>Upregulation of PLPP4 expression was observed in BC tissues and cells. Downregulation of PLPP4 expression in BC cells resulted in a suppression of their proliferative capacity, as well as a reduction in migratory and invasive capabilities. Additionally, this manipulation enhanced cell susceptibility to apoptosis and improved the sensitivity of these cells to DOX. When PLPP4 was knocked down in vivo in transplantable tumors, there was a marked enhancement in the responsiveness to DOX treatment. The transcription factor CAPRIN1 was found to regulate the expression of PLPP4 in the HCC1937 and MDA-MB-231 cell lines. Upregulation of CAPRIN1 was observed in both BC tissues and cells, and overexpression of PLPP4 reversed the effects of CAPRIN1 silencing on BC cell proliferation, migration, invasion, apoptosis, and DOX sensitivity.</p><p><strong>Conclusion: </strong>This study demonstrates that CAPRIN1 transcriptionally activates PLPP4 to inhibit DOX sensitivity and promote BC progression. Targeting PLPP4 may represent a novel therapeutic strategy to enhance the efficacy of DOX in BC patients.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2035-2045"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-elemene Ameliorates Cisplatin Resistance of Gastric Cancer via Regulating Exosomal METTL3-m6A-ARF6 Axis.","authors":"Huicong Song, Xuefeng Sun, Xiaohua Wang, Tianhai Xie, Zhihui Zheng, Ying Ji, Yanyan Cui","doi":"10.1007/s12013-024-01615-z","DOIUrl":"10.1007/s12013-024-01615-z","url":null,"abstract":"<p><p>The medial overall survival is low in patients with gastric cancer (GC) at advanced stage, in which drug resistance plays an important role. β-elemene has been established as the suppressed role on GC cell proliferation, however, the concrete mechanism of it remains unclear in cisplatin (DDP)-resistance GC. Cell counting kit-8 (CCK8) assay was used to measure the half maximal inhibitory concentration (IC₅₀) values of DDP in DDP-resistance GC cell lines. Cell apoptotic rates and invasive ability were tested by flow cytometry and transwell assay. Western blot and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to detect the protein and mRNA levels of methyltransferase like-3 (METTL3) and ADP ribosylation factor 6 (ARF6). SRAMP websites and methylated RNA immunoprecipitation (MeRIP) assay were applied to predicted m6A sites and verified m6A levels of ARF6 respectively. RNA immunoprecipitation (RIP) was used to explore the interaction between these two molecules. Xenograft tumor models were constructed to demonstrate the effects of β-elemene in vivo. β-elemene improved drug sensitivity and curbed malignant cell activities of DDP-resistance GC cells in vitro. ARF6 was upregulated in DDP-resistance GC cells and tissues, and its overexpression could abrogate the effects on DDP-resistant GC cells mediated by β-elemene treatment. Intracellular and exosomal METLL3 expression were elevated in and from DDP-resistance GC cell lines. Exosomal METTL3 released from DDP-resistance GC cells could counteract the effects of β-elemene on DDP-resistance GC cells partly via regulating ARF6 expression in the m6A-dependent manner. β-elemene could suppress DDP-resistance tumor growth in vivo. In conclusion, β-elemene could repress tumor growth and drug resistance via exosomal METTL3-m6A-ARF6 axis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2047-2058"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 Food Deprivation on Plasma Cortisol, Carbohydrate Metabolism, and Histomorphology in Clarias batrachus.","authors":"Shifali Hafeez, Fauzia Anwar Sherwani","doi":"10.1007/s12013-024-01645-7","DOIUrl":"10.1007/s12013-024-01645-7","url":null,"abstract":"<p><p>The nutritional status of fish is essential for its health, experimental studies, and aquaculture practices. The current study investigated the impact of food deprivation on biochemical parameters, histology of skin, gill, and kidney tissues, and ultrastructure of gills in Clarias batrachus. Fish were subjected to food deprivation for 2, 7, and 15 days resulting in (a) significant increase in plasma cortisol levels, (b) no significant changes in plasma osmolality and plasma glucose content, and (c) significant decrease in liver and muscle glycogen contents. A substantial damage was detected in skin, gill, and kidney tissues with histological alterations in a time-dependent manner. Skin tissue displayed melanomacrophage aggregation, excoriated epidermis and dermis. In gill tissue, epithelial lifting, edema, desquamation, deformed secondary lamellae, and lamellar hyperplasia were observed. Kidney tissue exhibited degenerated tubules, melanomacrophage aggregations, and shrunken renal tubule. Scanning electron microscopy revealed that food deprivation-induced marked presence of mucus, chloride cells, and pavement cells with well-defined microridges and microbridges following 2 days, opening of chloride cells was more prominent after 7 days, while more mucus secretion was observed after 15 days. After food deprivation, alterations in biochemical and histological parameters, and ultrastructural changes in target tissues reflect physiological and morphological disturbances in fish. The novelty of this study is that these parameters can be considered as biomarkers of feeding stress in fish and fish health and can provide important insights for better aquaculture practices.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2333-2348"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect and Mechanism of Vitamin D on Inflammatory Factors and Neutrophil Activity in Preterm Placenta of Rats Induced by LPS.","authors":"Danlin Yang, Xian Chen, Bingqing Lv","doi":"10.1007/s12013-024-01663-5","DOIUrl":"10.1007/s12013-024-01663-5","url":null,"abstract":"<p><p>To investigate the impact mechanisms of vitamin D on inflammatory factors and neutrophil activity in preterm pregnant rats. 24 pregnant rats were selected as the research objects and randomly divided into control group, LPS group and LPS + VD group, with 8 rats in each group. On the second day of pregnancy, the LPS + VD group was injected intraperitoneally with 50 mg/L vitamin D30.2 mL, and the LPS group and the control group were injected with the same amount of 0.9% NaCl twice a day. On the seventh day of pregnancy, the LPS group and the LPS + VD group were injected with 0.2 mL LPS into the tail vein to establish a preterm labor model induced by infection. The control group was injected with the same amount of physiological saline into the tail vein. Placental tissues from rats in the LPS + VD group and the LPS group were collected, and the expression levels of inflammatory factors TGF-β1, TNF-α, and VDBP were detected by immunohistochemistry. At the same time, serum IL-2 concentration was measured by ELISA and radioimmunoassay, the activity of neutrophils was evaluated by flow cytometry, and the expression of Hippo-YAP signaling pathway protein was detected by Western blot. Compared with the control group, the content of TNF-α, VDBP, and TGF-β1 in placenta in LPS group were higher than that in the control group (P < 5); Compared with the LPS group, the contents of TNF-α, BP and TGF-β1 in the LPS+VD group were significantly reduced,(P < 0.05); Compared with the control group, the serum IL-2 concentration in the LPS group was significantly higher than that in the control group (P < 0.05); Compared with the LPS group, the serum IL-2 concentration in the LPS + VD group decreased significantly (P < 0.05); Compared with the control group, the neutrophil ratio and absolute neutrophil value in the LPS group were higher than those in the control group (P < 0.05); Compared with the LPS group, the neutrophil ratio and absolute value of neutrophils decreased (P < 0.05); compared with the control group, the expression levels of YAP and P-YAP protein in the LPS group increased (P < 0.05); compared with the LPS group, the expression levels of YAP and P-YAP protein in the LPS + VD group decreased (P < 0.05). Vitamin D can improve the immune status of preterm pregnant mice by inhibiting the expression of placental inflammatory factors.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"2547-2552"},"PeriodicalIF":1.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mediating Role of Plasma Inflammatory Proteins in Gut Microbiota-Driven Valvular Heart Disease: A Mendelian Randomization Study.","authors":"Jiajing Zhao, Yuhan Wang, Chuxin Lv, Jiang Peng, Shu Lu, Lijuan Shen","doi":"10.1007/s12013-025-01780-9","DOIUrl":"https://doi.org/10.1007/s12013-025-01780-9","url":null,"abstract":"<p><p>This study investigates the causal relationships between gut microbiota (GM), plasma inflammatory proteins (PIPs), and valvular heart disease (VHD) using two-sample Mendelian Randomization (MR) analysis. We also assess whether PIPs mediate the link between GM and VHD. We conducted bidirectional MR analyses to explore causal associations between GM, PIPs, and VHD, and used multivariable MR to test the independence of associations. Genome-wide association study (GWAS) data on 196 GM taxa, 91 PIPs, and VHD were analyzed. MR methods including inverse-variance weighted (IVW), MR-Egger regression, and weighted median approaches were applied. Sensitivity analyses ensured robustness. Actinobacteria and Defluviitaleaceae were associated with lower VHD risk, while Oxalobacteraceae increased risk. At the genus level, Intestinibacter, Lachnospiraceae NC2004 group, Oscillospira, and Ruminococcaceae UCG004 were protective, whereas Oscillibacter increased risk. Among PIPs, Interleukin-10, Interleukin-17C, Leukemia inhibitory factor receptor (LIFR), and monocyte chemoattractant protein 2 were protective, while TNF-beta elevated risk. Multivariable MR confirmed the independent roles of TNF-beta, LIFR, and MCP-2. Actinobacteria's protective effect appeared partially mediated through increased LIFR expression, accounting for 14% of the effect. Our findings suggest that modulating gut microbiota, particularly enhancing Actinobacteria, may serve as a novel strategy for VHD prevention and treatment.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Polyphenols-mediated Squalene Epoxidase Inhibition: Computational Models and Experimental Validation for Targeting Cholesterol Biosynthesis.","authors":"Emadeldin M Kamel, Ahmed A Allam, Hassan A Rudayni, Saleh Alkhedhairi, Faris F Aba Alkhayl, Maha A Alwaili, Al Mokhtar Lamsabhi","doi":"10.1007/s12013-025-01784-5","DOIUrl":"https://doi.org/10.1007/s12013-025-01784-5","url":null,"abstract":"<p><p>Squalene epoxidase is a key enzyme in sterol biosynthesis, particularly in cholesterol metabolism. Its inhibition has emerged as a promising therapeutic strategy for metabolic disorders, hypercholesterolemia, and certain infections. Herein, we investigated the SQLE inhibitory potential of six polyphenolic compounds, identified through in silico virtual screening of a large natural phenolic library and selected for high predicted binding affinity and structural diversity. Molecular docking demonstrated strong interactions between these candidates and SQLE, with curcumin exhibiting the highest binding affinity (-10.1 kcal/mol). Molecular dynamics simulations confirmed stable interactions for all compounds, highlighting curcumin, piceatannol, and pterostilbene as particularly favorable. Their strong binding free energies were further supported by MM/PBSA calculations (-36.62 ± 4.17, -31.32 ± 3.77, and -32.01 ± 1.34 kcal/mol, respectively), corroborated by free energy landscape analysis. ADMET profiling revealed diverse pharmacokinetic properties among the six polyphenolics. In vitro testing confirmed curcumin as the most potent inhibitor (IC₅₀ = 1.88 ± 0.21 µM), with piceatannol (2.55 ± 0.30 µM) and pterostilbene (2.69 ± 0.11 µM) following closely. Enzyme kinetics demonstrated that these three compounds act as competitive inhibitors targeting the enzyme's active site. Collectively, these findings highlight the combined power of computational and experimental approaches for identifying novel SQLE inhibitors.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WTAP-induced m⁶A Methylation of Atoh8 Promotes Cell Proliferation and Fibrosis in Diabetic Nephropathy.","authors":"Suyu Wang, Henglu Zhang, Bingru Fei, Mei Zhang","doi":"10.1007/s12013-025-01778-3","DOIUrl":"https://doi.org/10.1007/s12013-025-01778-3","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a common diabetic complication, which increases morbidity of end-stage renal failure. N6-methyladenosine (m6A) modification has been reported in association with multiple physiological processes, however, its role in diabetic nephropathy is still poorly understood. Here, we found that the levels of m6A modification were up-regulated in both high-glucose-cultured mouse mesangial cells and the renal tissues from db/db mice. The key methyltransferase WT1 associated protein (WTAP) was primarily responsible for the elevated m6A modification. Moreover, WTAP knockdown significantly inhibited the proliferation and fibrosis of mouse mesangial cells (MMCs). Mechanistically, using the combination analysis of MeRIP-Seq and RNA-Seq, we revealed that Atoh8 was a downstream target of WTAP-induced m6A modification. We first revealed that Atoh8 was lowly expressed in renal tissues of DN model mice and HG-induced mesangial cells. WTAP reduced Atoh8 expression by inhibiting Atoh8 mRNA stability. Overexpression of Atoh8 restrained the proliferation and fibrosis of mesangial cells. This study provides novel insights into the role of m6A modification in DN and suggests that WTAP and Atoh8 could serve as potential therapeutic targets for this condition.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}