FEBS Open BioPub Date : 2024-10-29DOI: 10.1002/2211-5463.13891
Shehnaz Bano, Shyam More, Dattatray S. Mongad, Abdul Khalique, Dhiraj P. Dhotre, Manoj K. Bhat, Vasudevan Seshadri
{"title":"Prolonged exposure to insulin might cause epigenetic alteration leading to insulin resistance","authors":"Shehnaz Bano, Shyam More, Dattatray S. Mongad, Abdul Khalique, Dhiraj P. Dhotre, Manoj K. Bhat, Vasudevan Seshadri","doi":"10.1002/2211-5463.13891","DOIUrl":"10.1002/2211-5463.13891","url":null,"abstract":"<p>Glucose homeostasis is maintained by insulin. Insulin resistance is caused by multiple factors including hereditary factors and diet. The molecular mechanism underlying insulin resistance (IR) is not completely understood. Hyperinsulinemia often precedes insulin resistance and Type 2 diabetes. We had previously shown that prolonged exposure of insulin-responsive cells to insulin in the absence of high levels of glucose led to insulin resistance. In the present study, we show that the underlying cause for the impaired insulin signalling is the defective PI3K/AKT pathway. The observed insulin resistance is likely due to epigenetic alterations, as it can be maintained for several generations even when insulin is not provided, and epigenetic modifiers can reverse it. We also show that liver cell line (BRL-3A) developed impaired insulin signalling upon prolonged exposure to insulin in the absence of high levels of glucose. Transcriptomic analysis of the insulin-sensitive and resistance cells uncover altered signalling networks involved in chromatin remodelling, Rho GTPases, and ubiquitination. Furthermore, trimethylation of histone H3 at lysine 4 (H3K4me3) is increased in insulin-resistant cells. We extended these studies to mice, and show that mice injected with low doses of insulin when fasting develop insulin resistance with impaired glucose tolerance and increased HOMA-IR index. Altogether, these findings suggest that dysregulated synthesis of insulin in the absence of glucose stimulus could lead to epigenetic alterations that may ultimately result in insulin resistance.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"81-93"},"PeriodicalIF":2.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-27DOI: 10.1002/2211-5463.13917
Sunyoung Shin, Dongmin Kim, Hyemi Kim, Won-Ho Cho, Gyungmin Kim, Joon-Kyu Lee
{"title":"Interaction of RECQL4 with poly(ADP-ribose) is critical for the DNA double-strand break response in human cells","authors":"Sunyoung Shin, Dongmin Kim, Hyemi Kim, Won-Ho Cho, Gyungmin Kim, Joon-Kyu Lee","doi":"10.1002/2211-5463.13917","DOIUrl":"10.1002/2211-5463.13917","url":null,"abstract":"<p>To overcome genotoxicity, cells have evolved powerful and effective mechanisms to detect and respond to DNA lesions. RecQ Like Helicase-4 (RECQL4) plays a vital role in DNA damage responses. RECQL4 is recruited to DNA double-strand break (DSB) sites in a poly(ADP-ribosyl)ation (PARylation)-dependent manner, but the mechanism and significance of this process remain unclear. Here, we showed that the domain of RECQL4 recruited to DSBs in a PARylation-dependent manner directly interacts with poly(ADP-ribose) (PAR) and contains a PAR-binding motif (PBM). By replacing this PBM with a PBM of hnRNPA2 or its mutated form, we demonstrated that the PBM in RECQL4 is required for PARylation-dependent recruitment and the roles of RECQL4 in the DSB response. These results suggest that the direct interaction of RECQL4 with PAR is critical for proper cellular response to DSBs and provide insights to understand PARylation-dependent control of the DSB response and cancer therapeutics using PARylation inhibitors.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"140-150"},"PeriodicalIF":2.8,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-inflammatory properties of ophioglonin derived from the fern Ophioglossum vulgatum L. via inactivating NF-κB and MAPK signaling pathways","authors":"Xiaoqing Zhu, Cheng Tian, Dan Yao, Siqi Li, Junjiang Lv, Yongwen Chen, Xiaoyong Huang","doi":"10.1002/2211-5463.13914","DOIUrl":"10.1002/2211-5463.13914","url":null,"abstract":"<p>Medicinal plants contain bioactive compounds that have therapeutic effects on human health. <i>Ophioglossum vulgatum</i> L. is a representative species of the fern genus <i>Ophioglossum</i> that has anti-inflammatory properties as recognized in folk medicine. Herein, we performed a nitric oxide (NO) assay-guided screening in RAW264.7 cells to investigate the active components of the plant. We found that <i>ophioglonin</i> (OPN), a characteristic homoflavonoid of the genus <i>Ophioglossum</i>, is one of the bioactive components. Therefore, we performed a comparative analysis of the isolated compounds and found that OPN has effects similar to those of isolated dihydroquercetin and luteolin at the concentrations tested. The antioxidant and anti-inflammatory activities of OPN were extensively validated using lipopolysaccharide -stimulated RAW264.7 cells, mouse bone marrow-derived macrophages (BMDMs), and peritoneal exudate macrophages (PEMs). <i>In vivo</i> experiments with a carrageenan-induced mouse paw edema model further confirmed the anti-inflammatory effect of OPN. Additionally, we found that OPN and <i>Ophioglossum vulgatum</i> extracts inhibit the activation of signal transducers, NF-ĸB p65, IĸBα, ERK, p38, and JNK, consistent with the findings of pathway enrichment analysis. This work reinforces the anti-inflammatory properties of <i>Ophioglossum vulgatum</i> and indicates that OPN is a promising therapeutic agent for inflammation-associated disorders. Further clinical evaluations, including clinical trials, would be beneficial to validate the anti-inflammatory properties of OPN.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"122-139"},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-20DOI: 10.1002/2211-5463.13913
Barbora Kaščáková, Anna Koutská, Michaela Burdová, Petra Havlíčková, Ivana Kutá Smatanová
{"title":"Revealing protein structures: crystallization of protein-ligand complexes – co-crystallization and crystal soaking","authors":"Barbora Kaščáková, Anna Koutská, Michaela Burdová, Petra Havlíčková, Ivana Kutá Smatanová","doi":"10.1002/2211-5463.13913","DOIUrl":"10.1002/2211-5463.13913","url":null,"abstract":"<p>Protein crystallogenesis represents a key step in X-ray crystallography studies that employ co-crystallization and ligand soaking for investigating ligand binding to proteins. Co-crystallization is a method that enables the precise determination of binding positions, although it necessitates a significant degree of optimization. The utilization of microseeding can facilitate a reduction in sample requirements and accelerate the co-crystallization process. Ligand soaking is the preferred method due to its simplicity; however, it requires careful control of soaking conditions to ensure the successful integration of the ligands. This research protocol details the procedures for co-crystallization and soaking to achieve protein–ligand complex formation, which is essential for advancing drug discovery. Additionally, a simple protocol for demonstrating soaking for educational purposes is described.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 4","pages":"542-550"},"PeriodicalIF":2.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-14DOI: 10.1002/2211-5463.13889
Hale Gök Dağıdır, Neslihan Bukan, Meltem Bahcelioglu, Ayşen Çalıkuşu, Ece Alim, Saadet Özen Dizakar, Elif Topa, Hayrunnisa Bolay
{"title":"tVNS alters inflammatory response in adult VPA-induced mouse model of autism: evidence for sexual dimorphism","authors":"Hale Gök Dağıdır, Neslihan Bukan, Meltem Bahcelioglu, Ayşen Çalıkuşu, Ece Alim, Saadet Özen Dizakar, Elif Topa, Hayrunnisa Bolay","doi":"10.1002/2211-5463.13889","DOIUrl":"10.1002/2211-5463.13889","url":null,"abstract":"<p>Autism is a neurodevelopmental disorder with limited treatment alternatives and which incidence is increasing. Some research suggests that vagus nerve simulation might lead to the reduction of certain symptom. Therefore, we aimed to examine the effect of bilateral transcutaneous auricular vagus nerve stimulation (tVNS) on the inflammatory response in an adult valproic acid (VPA) induced mouse (C57BL6) model of autism for the first time. The autism model was induced by oral VPA administration (600 mg·kg<sup>−1</sup>) to C57BL/6 pregnant mice on E12.5 days. The study included three groups: the VPA Transcutaneous Auricular Stimulation Group (VPA + tVNS), the VPA Control Group (VPA + sham), and the Healthy Control Group (Control + sham). Each group included 16 mice (8 M/8 F). Our results show that serum IL-1β and IL-6 levels were significantly higher in male VPA-exposed mice than controls. However, IL-1β was significantly lower, and IL-6, TNF- α, and IL-22 were not different in female VPA-exposed mice compared to the control group. Brain NLRP3 levels were significantly higher in both sexes in the VPA autism model (<i>P</i> < 0.05). tVNS application increased brain NLRP3 levels in both sexes and reduced serum IL-1β levels in male mice. We conclude that cytokine dysregulation is associated with the VPA-induced adult autism model, and the inflammatory response is more pronounced in male mice. tVNS application altered the inflammatory response and increased brain NLPR3 levels in both sexes. Further studies are needed to understand the beneficial or detrimental role of the inflammatory response in autism and its sexual dimorphism.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 1","pages":"69-80"},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-14DOI: 10.1002/2211-5463.13908
Mariana Valério, Carolina C. Buga, Manuel N. Melo, Cláudio M. Soares, Diana Lousa
{"title":"Viral entry mechanisms: the role of molecular simulation in unlocking a key step in viral infections","authors":"Mariana Valério, Carolina C. Buga, Manuel N. Melo, Cláudio M. Soares, Diana Lousa","doi":"10.1002/2211-5463.13908","DOIUrl":"10.1002/2211-5463.13908","url":null,"abstract":"<p>Viral infections are a major global health concern, affecting millions of people each year. Viral entry is one of the crucial stages in the infection process, but its details remain elusive. Enveloped viruses are enclosed by a lipid membrane that protects their genetic material and these viruses are linked to various human illnesses, including influenza, and COVID-19. Due to the advancements made in the field of molecular simulation, significant progress has been made in unraveling the dynamic processes involved in viral entry of enveloped viruses. Simulation studies have provided deep insight into the function of the proteins responsible for attaching to the host receptors and promoting membrane fusion (fusion proteins), deciphering interactions between these proteins and receptors, and shedding light on the functional significance of key regions, such as the fusion peptide. These studies have already significantly contributed to our understanding of this critical aspect of viral infection and assisted the development of effective strategies to combat viral diseases and improve global health. This review focuses on the vital role of fusion proteins in facilitating the entry process of enveloped viruses and highlights the contributions of molecular simulation studies to uncover the molecular details underlying their mechanisms of action.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"15 2","pages":"269-284"},"PeriodicalIF":2.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-13DOI: 10.1002/2211-5463.13904
Sang-Eun Lee, Soomin Park, Rian Kang, Taehoon Lee, Won Jong Yu, Sunghoe Chang, Jong-Chan Park
{"title":"Hippocampal tau-induced GRIN3A deficiency in Alzheimer's disease","authors":"Sang-Eun Lee, Soomin Park, Rian Kang, Taehoon Lee, Won Jong Yu, Sunghoe Chang, Jong-Chan Park","doi":"10.1002/2211-5463.13904","DOIUrl":"10.1002/2211-5463.13904","url":null,"abstract":"<p>Alzheimer's disease (AD) is characterized by significant alterations in hippocampal function and structure, but the molecular mechanisms underlying the hippocampal region remain elusive. We integrated multiple transcriptome datasets including human or rat hippocampus (GSE173955, GSE129051, GSE84422) to identify candidate genes. Subsequent analyses including gene ontology analysis and protein–protein interaction mapping were performed to identify key genes and pathways. We found that glutamate ionotropic receptor NMDA-type subunit 3A (<i>GRIN3A</i>) and glutamate metabotropic receptor 8 (<i>GRM8</i>), which are related to the glutamatergic system, were the top two annotated genes and directly related to <i>MAPT</i>, which encodes a tau protein. Since there is no direct evidence of interaction between tauopathy and these genes in AD, further transcriptomic data (GSE125957, GSE56772) from tau transgenic mice and experimental validations through primary rat hippocampal neurons and induced pluripotent stem cell (iPSC)-derived brain organoids were performed. Interestingly, we identified that decreased NR3A (encoded by <i>GRIN3A</i>) and mGluR8 (encoded by <i>GRM8</i>) are correlated with tauopathy and loss of postsynaptic function in AD. Taken together, our results identified a novel tauopathy biomarker <i>GRIN3A</i> in AD. Furthermore, our findings suggest that an integrated approach combining public databases and diverse experimental validations can contribute to the advancement of precision medicine therapies.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 12","pages":"2059-2071"},"PeriodicalIF":2.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13904","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-10DOI: 10.1002/2211-5463.13893
Geyao Dong, Tsuyoshi Nakai, Tetsuo Matsuzaki
{"title":"A novel plasmid-based experimental system in Saccharomyces cerevisiae that enables the introduction of 10 different plasmids into cells","authors":"Geyao Dong, Tsuyoshi Nakai, Tetsuo Matsuzaki","doi":"10.1002/2211-5463.13893","DOIUrl":"10.1002/2211-5463.13893","url":null,"abstract":"<p>The budding yeast <i>Saccharomyces cerevisiae</i> is commonly used as an expression platform for the production of valuable compounds. Yeast-based genetic research can uniquely utilize auxotrophy in transformant selection: auxotrophic complementation by an auxotrophic marker gene on exogenous DNA (such as plasmids). However, the number of required auxotrophic nutrients restricts the number of plasmids maintained by the cells. We, therefore, developed novel Δ10 strains that are auxotrophic for 10 different nutrients and new plasmids with two multiple cloning sites and auxotrophic markers for use in Δ10 strains. We confirmed that Δ10 strains were able to maintain 10 types of plasmids. Using plasmids encoding model proteins, we detected the co-expression of 17 different genes in Δ10 cell lines. We also constructed Δ9 strains that exhibited auxotrophy for nine nutrients and increased growth compared to Δ10. This study opens a new avenue for the co-expression of a large number of genes in eukaryotic cells.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 12","pages":"1955-1971"},"PeriodicalIF":2.8,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS Open BioPub Date : 2024-10-09DOI: 10.1002/2211-5463.13906
Gustavo de Almeida Santos, Andrea N. B. Englund, Eirin L. Dalleywater, Åsmund Kjendseth Røhr
{"title":"Characterization of two bacterial tyrosinases from the halophilic bacterium Hahella sp. CCB MM4 relevant for phenolic compounds oxidation in wetlands","authors":"Gustavo de Almeida Santos, Andrea N. B. Englund, Eirin L. Dalleywater, Åsmund Kjendseth Røhr","doi":"10.1002/2211-5463.13906","DOIUrl":"10.1002/2211-5463.13906","url":null,"abstract":"<p>Tyrosinases (TYRs) are type-3 copper proteins that are widely distributed in nature. They can hydroxylate and oxidize phenolic molecules and are mostly known for producing melanins that confer protection against photo induced damage. TYRs are also thought to play an important role in the ‘latch mechanism’, where high concentrations of phenolic compounds inhibit oxidative decomposition of organic biomass and subsequent CO<sub>2</sub> release, especially relevant in wetland environments. In the present study, we describe two TYRs, <i>Hc</i>Tyr1 and <i>Hc</i>Tyr2, from halophilic bacterium <i>Hahella</i> sp. CCB MM4 previously isolated at Matang mangrove forest in Perak, Malaysia. The structure of <i>Hc</i>Tyr1 was determined by X-ray crystallography at a resolution of 1.9 Å and represents an uncharacterized group of prokaryotic TYRs as demonstrated by a sequence similarity network analysis. The genes encoding the enzymes were cloned, expressed, purified and thoroughly characterized by biochemical methods. <i>Hc</i>Tyr1 was able to self-cleave its lid-domain (LID) in a protease independent manner, whereas the LID of <i>Hc</i>Tyr2 was essential for activity and stability. Both enzymes showed variable activity in the presence of different metals, surfactants and NaCl, and were able to oxidize lignin constituents. The high salinity tolerance of <i>Hc</i>Tyr1 indicates that the enzyme can be an efficient catalyst in the habitat of the host.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 12","pages":"2038-2058"},"PeriodicalIF":2.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TGF-β effects on adipogenesis of 3T3-L1 cells differ in 2D and 3D cell culture conditions","authors":"Araya Umetsu, Megumi Watanabe, Tatsuya Sato, Megumi Higashide, Nami Nishikiori, Masato Furuhashi, Hiroshi Ohguro","doi":"10.1002/2211-5463.13890","DOIUrl":"10.1002/2211-5463.13890","url":null,"abstract":"<p>The TGF-β superfamily plays a pivotal role in the regulation of adipogenesis, but little is known about the potential differential role of the three isoforms of TGF-β, TGF-β-1~3. To further elucidate their role, two-dimensionally (2D) and three-dimensionally (3D) cultured 3T3-L1 mouse preadipocytes were subjected to the following analyses: (a) qPCR analysis of adipogenesis-related factors and major extracellular matrix protein (2D and /or 3D), (b) lipid staining by Oil Red O (2D) or BODIPY (3D), (c) Seahorse cellular metabolic measurement (2D), and (d) size and stiffness measurements of 3D 3T3-L1 spheroids. In the 2D cultured 3T3-L1 cells, mRNA expression levels of adipogenesis-related genes and Oil Red O lipid staining intensity were significantly increased by adipogenesis and they were substantially decreased following treatment with 0.1 n<span>m</span> TGF-β isoforms, with TGF-β2 having the greater effects. Consistent with these results, treatment with TGF-β2 resulted in suppression of mitochondrial and glycolytic functions in 2D cultured 3T3-L1 cells. However, the inhibitory effect of TGF-β on adipogenesis decreased under 3D spheroid culture conditions and TGF-β isoforms did not affect adipogenesis-induced (a) enlargement and downsizing of 3T3-L1 spheroids, (b) increase in BODIPY lipid staining intensity, and (c) up-regulation of the mRNA expression of adipogenesis-related genes. The findings presented herein suggest that the three TGF-β isoforms have different suppressive effects on adipogenesis-related cellular properties of 2D cultured 3T3-L1 cells and that their effects decrease under 3D spheroid culture conditions.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":"14 12","pages":"2026-2037"},"PeriodicalIF":2.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/2211-5463.13890","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}