Molecular and Cellular Biochemistry最新文献

{"title":"Wogonin alleviates inflammation caused by neutrophil extracellular traps in atopic dermatitis via miR-4667-5p/CCL2 pathway.","authors":"Fen Qian, Yan Song, Zhihua Wu","doi":"10.1007/s11010-026-05711-x","DOIUrl":"10.1007/s11010-026-05711-x","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is primarily characterized by dysregulation of the immune system and abnormal inflammation. Dictamni Cortex is an herb used in traditional Chinese medicine to treat damp-heat skin diseases. To excavate the effective component of Dictamni Cortex for treating AD and explore the specific molecular mechanism. First, wogonin was screened from the active constituents of Dictamnus cortex, and CCL2 was identified as a candidate hub gene by constructing an herb-ingredient-gene network. The AD cell model was constructed using human epidermal keratinocytes (HEKs), and the AD mouse model was employed to investigate the therapeutic efficacy of wogonin. The effect of HEKs on neutrophil extracellular trap (NET) formation under pathological conditions was explored through co-culture experiments. The conditional medium containing NETs was used to treat HEKs to investigate AD-associated inflammatory alterations. Through bioinformatics means, miR-4667-5p was predicted as an upstream regulator targeting CCL2 mRNA, and this was validated via RNA pull-down and dual-luciferase reporter assays. CCL2 was significantly upregulated in the AD cell model, which mediated the functional damage of HEKs under AD pathological conditions. Wogonin not only rescued the cell viability of HEKs in a concentration-dependent manner by inhibiting CCL2 but also alleviated the AD-related inflammation in vitro and in vivo. Within the co-culture system, AD model cells recruited neutrophils and induced NET formation, which was suppressed following CCL2 knockdown. Overexpression of miR-4667-5p suppressed CCL2 expression by targeting its mRNA and alleviated inflammation in HEKs induced by NET-conditioned medium. This inflammation was also suppressed by wogonin treatment. The miR-4667-5p antagonist weakened this therapeutic effect of wogonin, which was rescued by the silencing of CCL2. Under AD pathological conditions, HEKs promoted NET formation, which in turn exacerbated inflammation within HEKs. Wogonin treatment rescued this inflammatory damage by modulating the miR-4667-5p/CCL2 pathway.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5251-5262"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYBL2 promotes malignant phenotypes and M2-like macrophage polarization through CCL2 in non-small cell lung cancer.","authors":"Qiong Sun, Jing Meng, Rochelle McGowan, Belinda Hodge, Daniel Shan, Nicolas Miller, Weiwei Shi","doi":"10.1007/s11010-026-05733-5","DOIUrl":"10.1007/s11010-026-05733-5","url":null,"abstract":"<p><p>Hub genes associated with non-small cell lung cancer (NSCLC) were identified through bioinformatics screening. In vitro experiments analyzed the potential mechanisms by which these genes regulate tumor malignant phenotypes and macrophage polarization. Differentially expressed genes were identified from The Cancer Genome Atlas (TCGA)-NSCLC and GSE32175 datasets, followed by protein-protein interaction (PPI) network analysis to screen hub genes. The effects of MYB Proto-Oncogene Like 2 (MYBL2) on NSCLC progression and macrophage polarization were evaluated using in vitro models. The regulatory relationship between MYBL2 and C-C motif chemokine ligand 2 (CCL2) was investigated by Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays, and rescue experiments were performed to validate the role of the MYBL2-CCL2 axis. Bioinformatics screening identified BUB1B, CDCA2 and MYBL2 as key hub genes with high expression in NSCLC, among which MYBL2 was significantly upregulated in NSCLC cells. Functional experiments confirmed that MYBL2 silencing markedly inhibited the malignant proliferation, migration and invasion of NSCLC cells. Tumor cell MYBL2 knockdown effectively reversed M2-like polarization and promoted M1-like polarization in the co-culture system. Mechanistically, MYBL2 directly bound to the CCL2 promoter region to enhance CCL2 transcriptional activity and upregulate CCL2 expression in NSCLC cells. Exogenous CCL2 supplementation significantly rescued the inhibitory effect of MYBL2 knockdown on macrophage M2-like polarization, verifying the mediating role of CCL2 in this regulatory axis. MYBL2 is strongly expressed in NSCLC cells and is associated with enhanced malignant phenotypes. It may affect macrophage M2-like polarization by upregulating CCL2, thus participating in NSCLC immune microenvironment remodeling.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5385-5396"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligustrazine with telmisartan mitigates the progression of diabetic cardiomyopathy by reducing ER stress, apoptosis, and myocardial fibrosis.","authors":"Mansi Vinodkumar Trivedi, Hemant R Jadhav, Anil Bhanudas Gaikwad","doi":"10.1007/s11010-026-05740-6","DOIUrl":"10.1007/s11010-026-05740-6","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a condition whereby hyperglycemia induces structural, functional, and metabolic changes in the heart, leading to cardiac dysfunction. The renin-angiotensin system plays a pivotal role in the progression of DCM. Ligustrazine (LIG) is an alkaloid from the Chuanxiong plant that has long been used as a \"food medicine\". The stewed rhizomes, which contain LIG as a major constituent, have proven benefits and have been extensively studied for their anti-apoptotic and anti-fibrotic properties; however, their role in DCM remains unclear. Additionally, whether combining LIG with telmisartan (TEL), an AT1R blocker, offers greater cardiac protection is unclear. The animal experimentation included a single streptozotocin-55 mg/kg, i.p. injection for disease induction. Four weeks post-induction, animals received respective treatments for 4 weeks: Normal control (NC), diabetic control (DC), DC+LIG40 (40 mg/kg, i.p.), DC+LIG80 (80 mg/kg, i.p.), NC+LIG80, DC+T10 (10 mg/kg, p.o.), and DC+LIG40+ T5. The heart and blood samples were collected to assess cardiac markers, including LDH, CK-MB, ANP, and BNP. Cardiac electrical and hemodynamic changes, as well as histological, immunohistochemical, immunofluorescence, qRT-PCR, and apoptotic assays were performed. A combination of LIG40 and TEL5 provided greater cardiac protection, with a significant improvement in cardiac electrical rhythm and hemodynamics, accompanied by a marked reduction in UPR^ER, myocardial apoptosis, and fibrosis, indicating the efficacy of the combination therapy. Combining LIG, a phytopharmaceutical, with TEL offers greater efficacy in DCM, provides a novel therapeutic strategy, and is compelling and holds value in treating DCM.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5515-5532"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutrient deprivation enhances the cytotoxic effects of a sulfonamide-chalcone hybrid in PC-3 prostate cancer cells.","authors":"Gisele Santos de Araújo, Rodrigo Elísio de Sá, Stéphanie Aguiar de Negreiros Matos Silva, Fabrício Dos Santos Machado, Caridad Noda Perez, Mirian Rita Carrilho de Castro, Anali Del Milagro Bernabe Garnique, Bruna Oliveira de Almeida, Keli Lima, João Agostinho Machado Neto, Letícia Veras Costa Lotufo, José Delano Barreto Marinho Filho, Ana Jérsia Araujo","doi":"10.1007/s11010-026-05723-7","DOIUrl":"10.1007/s11010-026-05723-7","url":null,"abstract":"<p><p>Hybrid molecules integrating different pharmacophoric motifs have emerged as a promising strategy in anticancer drug discovery. In this study, we report for the first time the biological effects of a sulfonamide-chalcone hybrid in the PC-3 prostate cancer cell line under standard culture conditions and nutrient deprivation. The molecular design of SSC185 (µ-(2,5-dichloro-N-{4-[(3E)-4-(3-nitrophenyl)buta-1,3-dien-2-yl]phenyl}benzenesulfonamide) incorporates an α,β-unsaturated system conjugated to the chalcone scaffold together with a sulfonamide moiety, structural features frequently associated with modulation of cancer-related signaling pathways. Results demonstrated that SSC185 reduced the MTT signal of PC-3 cells in a concentration- and time-dependent manner, with IC₅₀ values of 24.69 µM at 24 h and 18.9 µM at 72 h, and exhibited enhanced activity under serum-deprived conditions, with an IC₅₀ of 4.20 µM. Complementary studies employing pharmacological modulators of autophagy, apoptosis, redox status, and proteostasis were conducted to further characterize the compound's activity. SSC185 increased SQSTM1/p62 and LC3B-I levels without detectable changes in LC3B-II levels or increased acidic vesicle formation, accompanied by reduced AKT/RPS6 signaling and mitochondrial dysfunction. These molecular alterations were associated with the cellular response to SSC185, while nutrient deprivation markedly enhanced its activity in PC-3 cells, indicating that the cellular nutritional context influences the response to the compound.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5397-5418"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of receptor-interacting protein kinases (RIP1 and RIP3) in the therapeutic effect of thymoquinone against rat testis ischemia/reperfusion.","authors":"Hatice Gülmez, Hüseyin İlbasmış, Hilal Akalın, Mustafa Ermiş, Derya Karabulut","doi":"10.1007/s11010-026-05756-y","DOIUrl":"10.1007/s11010-026-05756-y","url":null,"abstract":"<p><p>Torsion-induced ischemia causes lipid peroxidation in tissue, increases membrane permeability, and induces irreversible necroptosis in cells. The aim was to investigate the effects of thymoquinone (THQ) on receptor-interacting serine-threonine kinases (RIP1 and RIP3) after testicular torsion-induced ischemia/reperfusion (I/R). Control, ischemia/reperfusion (I/R), thymoquinone (THQ) 10 mg/kg and ischemia/reperfusion + thymoquinone (I/R+THQ). At the end of the experiment, spermiogram, histological and immunohistochemical, gene expression and biochemical analyses were performed on testicular tissue by collecting blood samples. Motility, testicular tissue seminiferous tubule epithelium thickness, tubule diameter and JTBS decreased in the I/R group compared to the Control and THQ groups.Both gene expression and immunoreactivity intensities of RIP1 and RIP3 increased in I/R. Furthermore, glial cell-derived neurotrophic factor (GDNF) and androgen-binding protein (ABP) decreased, steroidogenic acute regulatory protein (StAR), blood testosterone, and luteinizing hormone (LH) increased, and follicle-stimulating hormone (FSH) remained unchanged. THQ had a regulatory effect on all parameters. In addition to histopathological findings in testicular tissue, changes in RIP1, RIP3, GDNF, and StAR expression after I/R caused damage to both spermatogenic and non-spermatogenic tissue cell lines. Furthermore, changes in hormone levels indicate tissue dysfunction. The results reveal novel findings suggesting that THQ, applied after I/R, may be an effective compound for improving the structural and functional integrity of tissue; however, these findings need to be confirmed using various techniques with different application times and doses.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5761-5772"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"USP35-mediated NRF2 deubiquitination attenuates experimental cryptorchidism-induced testicular damage and H₂O₂-induced apoptosis and oxidative stress in spermatogonia.","authors":"Xiang Liu, Jing-Jing Sun, Chang-Kun Mao, Yong-Sheng Cao, Qi-Fei Deng, Guang-Yuan Li","doi":"10.1007/s11010-026-05707-7","DOIUrl":"10.1007/s11010-026-05707-7","url":null,"abstract":"<p><p>Cryptorchidism, characterized by the failure of one or both testes to descend into the scrotum, is the most prevalent urogenital malformation in male infants and an important risk element of male infertility and testicular cancer. The purpose of this study was to investigate the molecular mechanisms underlying cryptorchidism-induced testicular damage, with a focus on the role of USP35. Here we established a unilateral experimental cryptorchidism model of Sprague-Dawley rats by resetting the left testis to the abdominal cavity and suturing the inguinal canal, thus preventing its natural descent. The findings indicated that apoptosis and oxidative stress (OS) levels were increased in the undescended testis (UDT) compared to the descended testis (DT) group. Subsequent mRNA sequencing of DT and UDT tissues revealed that ubiquitin specific peptidase 35 (USP35) expression was downregulated in the UDT, implying that USP35 may be an important factor in the pathogenesis of cryptorchidism. To further investigate, an oxidative damage model was constructed using H₂O₂-treated GC-1 spermatogonia. USP35 expression was reduced in H₂O₂-exposed cells, while overexpression of USP35 attenuated H₂O₂-induced oxidative damage by inhibiting apoptosis and OS. Mechanistically, USP35 interacted with nuclear factor erythroid 2-related factor 2 (NRF2) and stabilized its protein expression via deubiquitination. Impairment of NRF2 function abolished the protective effect of USP35 against oxidative damage in H₂O₂-treated GC-1 spermatogonia. Overall, these results highlight the significance of the USP35-NRF2 axis in protecting spermatogonia from oxidative injury, suggesting that USP35 may be a potential therapeutic target against cryptorchidism-induced early germ cell damage.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5185-5199"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics analysis identifies LIPA as a prognostic hub and ferroptosis regulator in lung adenocarcinoma.","authors":"Fan Zhang, Shuai Han, Xiaodong Cao, Dan Pan, Weijie Song","doi":"10.1007/s11010-026-05741-5","DOIUrl":"10.1007/s11010-026-05741-5","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer mortality, underscoring the urgent need for biomarkers and therapeutic targets rooted in metabolic reprogramming. By integrating multi-omics analyses with experimental validation, we identified 67 lipid metabolism-related genes dysregulated in LUAD and constructed a five-gene prognostic signature via LASSO regression; lower expression of the signature genes correlated with poor survival. Single-cell and spatial transcriptomics revealed cell-type-specific dysregulation of the hub gene LIPA, which was upregulated in monocytes but downregulated in macrophages within the tumor microenvironment. Functional assays demonstrated that LIPA overexpression inhibited tumor proliferation in vitro and suppressed orthotopic tumor growth in vivo, at least in part through a ferroptosis-dependent mechanism involving TXNIP and ALOX5. Virtual screening further identified Castanospermine as a potential LIPA activator; treatment elevated LIPA expression, modulated the CD4+/CD8 + T-cell ratio, and attenuated tumor progression in mice. Collectively, these findings establish LIPA as a critical link between lipid metabolism, ferroptosis, and immune modulation in LUAD, and provide a prognostic signature for risk stratification as well as a candidate compound for targeting lipid metabolic vulnerabilities.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5563-5576"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro evaluation of hydroxyapatite, β-tricalcium phosphate, graphene oxide and zinc oxide for osteochondral regeneration under inflammatory conditions.","authors":"Roman Novotný, Izabella Rajzer, Jana Franková","doi":"10.1007/s11010-026-05728-2","DOIUrl":"10.1007/s11010-026-05728-2","url":null,"abstract":"<p><p>The repair of osteochondral defects is challenging due to differing regenerative capacities of bone and cartilage, a challenge that is often exacerbated by chronic inflammation. This study evaluated the immunomodulatory and regenerative potential of hydroxyapatite (HAp), β-tricalcium phosphate (β-TCP), graphene oxide (GO), and zinc oxide (ZnO) on osteoblast-like cells (Saos-2) and chondrocyte-like cells (SW1353) under IL-1β-induced inflammatory conditions. An MTT assay was used to measure cell viability at different concentrations of substances. To investigate the ability of Saos-2 cells to synthesize an inorganic extracellular matrix (ECM), mineralisation was observed via Alizarin Red staining and alkaline phosphatase (ALP) activity. The protein production of pro-COL1, pro-COL2, ACAN, MMP-9, IL-6, IL-8, BMP-2/4, RUNX2, and SOX9 was assessed using ELISA and Western blotting. The gene expression of RUNX2, SOX9, MMP-3, ADAMTS-5, COL10A1, ACAN, BGLAP, and FGF-2 was evaluated using RT-qPCR. Under inflammatory conditions, all the evaluated substances maintained basal matrix synthesis while suppressing the expression of ECM-degrading enzymes. Notably, GO exhibited a strong chondroprotective effect in SW1353 cells by significantly downregulating the expression of RUNX2 and FGF-2. Conversely, ZnO was found to impair mineralisation via the cytoplasmic trapping of RUNX2. Furthermore, their distinct impact on cellular phenotypes, ranging from GO-mediated chondroprotection to the inhibition of mineralisation by ZnO, highlights that the strategic, layer-specific integration of these substances is essential for actively guiding and sustaining the complex process of osteochondral healing. Consequently, our findings demonstrate a dual therapeutic benefit, in which the evaluated substances simultaneously suppress ECM degradation and support fundamental matrix synthesis under inflammatory stress.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5355-5371"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzo[a]pyrene-derived quinones exploit mitochondrial electron transport to drive catalytic redox cycling and potent ROS amplification.","authors":"Y Robert Li, Hong Zhu, Michael A Trush","doi":"10.1007/s11010-026-05736-2","DOIUrl":"10.1007/s11010-026-05736-2","url":null,"abstract":"<p><p>Benzo[a]pyrene (BP)-derived quinones are major oxidative metabolites of this ubiquitous environmental carcinogen, yet the mechanisms by which they generate reactive oxygen species (ROS) remain poorly understood. Here, we tested the hypothesis that BP-derived quinones exploit mitochondrial electron transport to undergo redox cycling and amplify ROS production. Using isolated mitochondria energized with either pyruvate/malate or succinate, we found that BP-1,6-quinone (BP-1,6-Q), BP-3,6-quinone (BP-3,6-Q), BP-6,12-quinone (BP-6,12-Q), and BP-7,8-quinone (BP-7,8-Q) stimulated potassium cyanide-resistant oxygen consumption, indicating active mitochondrial redox cycling. BP quinone redox cycling was accompanied by substantial production of superoxide and hydrogen peroxide, with BP-1,6-Q, BP-3,6-Q, and BP-6,12-Q exhibiting the greatest activity. Notably, BP-1,6-Q induced robust ROS generation at submicromolar concentrations, suggesting that mitochondria can serve as highly efficient amplifiers of BP quinone-mediated oxidative stress. Pharmacological dissection of the mitochondrial electron transport chain suggested complexes I and III as the principal sites supporting BP quinone redox cycling and ROS production, whereas the contributions of complexes II and IV were negligible. These findings indicate that BP-derived quinones exploit electron flow through mitochondrial complexes I and III to drive catalytic redox cycling and potent ROS amplification. This previously underappreciated mechanism provides a mechanistic link between BP metabolism, mitochondrial oxidative stress, and the pathogenesis of BP-associated toxicity.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5483-5494"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13687152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the murine preadipocytes differentiation by bitter taste receptor Tas2r108 and Tas2r126.","authors":"Eisuke Kato, Shota Oshima, Yusuke Adachi, Reitaro Imai","doi":"10.1007/s11010-026-05738-0","DOIUrl":"10.1007/s11010-026-05738-0","url":null,"abstract":"<p><p>Taste 2 receptors (T2Rs) are known as receptors for sensing bitterness, but their gene expressions are observed in various extraoral tissues. T2Rs in adipocytes have attracted attention because bitter compounds influence lipid accumulation. However, the role of T2Rs in adipocytes has not been extensively investigated. This study investigated the functions of Tas2r108 and Tas2r126 in preadipocyte differentiation. Overexpression of Tas2r108 or Tas2r126 inhibited the differentiation of 3T3-L1 cells and mouse primary preadipocytes. Similarly, knockdown of Tas2r108 suppressed the differentiation of these cells. Consistent with the knockdown results, stimulation with T2R agonists during the differentiation of 3T3-L1 cells enhanced adipogenesis. Mechanistic analysis revealed that the suppressed differentiation by T2R overexpression involves the downregulation of Cebpb, while T2R knockdown involves the upregulation of Nr4a2 and Nr4a3 and downregulation of Egr2. Analysis with T2R agonists revealed that T2Rs in preadipocytes couple with inhibitory G-protein to downregulate intracellular cAMP concentrations, which works through ERK to enhance adipogenesis. These results demonstrate the regulation of adipocyte differentiation by T2Rs and suggest that bitter compounds enhance adipogenesis via T2Rs.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":"5533-5544"},"PeriodicalIF":4.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}