Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"The intestine-specific homeobox (ISX) modulates β-carotene-dependent regulation of microsomal triglyceride transfer protein (MTP) in a tissue-specific manner","authors":"Youn-Kyung Kim ,&nbsp;Elena Giordano ,&nbsp;Ulrich Hammerling ,&nbsp;Dhruv Champaneri ,&nbsp;Johannes von Lintig ,&nbsp;M. Mahmood Hussain ,&nbsp;Loredana Quadro","doi":"10.1016/j.bbalip.2024.159584","DOIUrl":"10.1016/j.bbalip.2024.159584","url":null,"abstract":"<div><div>Vitamin A is an essential nutrient crucial to ensuring proper mammalian embryonic development. β-Carotene is the most prevalent form of vitamin A in food that, when transferred in its intact form from mother to the developing tissues, can serve as an <em>in situ</em> source of retinoic acid, the active form of vitamin A. We have previously provided evidence that the maternal-fetal transfer of β-carotene across the placenta is mediated by lipoproteins and that β-carotene itself regulates placenta lipoprotein biogenesis by means of its derivatives β-apo-10′-carotenoids and retinoic acid. These metabolites exert antagonistic transcriptional activity on placental microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB), two key players of lipoprotein biosynthesis. Here, we analyzed the time-dependency of this regulation over the course of 24 h upon a single maternal administration of β-carotene. We also tested the hypothesis that the transcriptional repressor intestine-specific homeobox (ISX) plays a role in the regulation of <em>Mttp</em> in placenta. We observed that ISX is expressed in placenta of mouse dams and is regulated by β-carotene availability. Furthermore, we demonstrated that the absence of <em>Isx</em> disrupts the β-carotene-mediated regulation of placental MTP. We also showed that this mechanism is organ-specific, as it was not observed in enterocytes of the intestine, a major place of <em>Isx</em> expression. Therefore, we identified ISX as a “master” regulator of a placental β-carotene-dependent transcriptional regulatory cascade that fine-tunes the flux of provitamin A carotenoid towards the developing fetus.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159584"},"PeriodicalIF":3.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790970","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":"PLAAT5 as an N-acyltransferase responsible for the generation of anti-inflammatory N-acylethanolamines in testis","authors":"Mohammad Mamun Sikder ,&nbsp;Sumire Sasaki ,&nbsp;Yoshimi Miki ,&nbsp;Yuki Nagasaki ,&nbsp;Ken-ichi Ohta ,&nbsp;Zahir Hussain ,&nbsp;Hiroyuki Saiga ,&nbsp;Mari Ohmura-Hoshino ,&nbsp;Katsuaki Hoshino ,&nbsp;Masaki Ueno ,&nbsp;Miki Okada-Iwabu ,&nbsp;Makoto Murakami ,&nbsp;Natsuo Ueda ,&nbsp;Toru Uyama","doi":"10.1016/j.bbalip.2024.159583","DOIUrl":"10.1016/j.bbalip.2024.159583","url":null,"abstract":"<div><div><em>N</em>-Acylethanolamines (NAEs) are a class of lipid mediators that exhibit anti-inflammatory and appetite-suppressive activities. Among them, palmitoylethanolamide (PEA) and arachidonoylethanolamide (AEA) bind to peroxisomal proliferator-activated receptor (PPAR) α and cannabinoid receptor CB1, respectively. <em>N</em>-Acyl-phosphatidylethanolamine (NAPE) as a precursor of NAEs is biosynthesized from membrane phospholipids by <em>N</em>-acyltransferases, which consist of group IVE cytosolic phospholipase A₂ε (cPLA₂ε) and PLAAT (phospholipase A and acyltransferase) family enzymes. While cPLA₂ε is responsible for the production of NAEs not only in specific tissues, including muscle, skin, and the stomach, but also under pathological conditions, such as psoriasis and brain ischemia, the involvement of the PLAAT family <em>in vivo</em> remains unclear. Considering the specific expression of PLAAT5 in testes, we investigated the potential role of PLAAT5 in the formation of NAEs in testes using PLAAT5-deficient (<em>Plaat5</em>^{<em>−/−</em>}) mice. High-performance liquid chromatography coupled with tandem mass spectrometry showed that PLAAT5 deficiency decreased the total level of NAEs by 61 %, with PEA and AEA being reduced by 64 % and 87 %, respectively. Following a treatment with cadmium chloride, an environmental toxin that induces testicular inflammation, the expression of inflammatory genes (<em>Il6</em>, <em>Tnf</em>, and <em>Nos2</em>) in testes was markedly higher in <em>Plaat5</em>^{<em>−/−</em>} mice than in <em>Plaat5</em>^<em>+/+</em> mice, and their expression was attenuated by the administration of PEA and AEA. Furthermore, these anti-inflammatory effects were canceled by a co-treatment with the antagonists of PPARα or CB1. These results suggest that PLAAT5 is responsible for the biosynthesis of anti-inflammatory NAEs in testes.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159583"},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725331","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":"Dysregulated mitochondrial fission and neurodegeneration proteomic signature in ACSF3-deficient cells","authors":"Khaled Alatibi ,&nbsp;Kathrin Sumser ,&nbsp;Maria Elpida Christopoulou ,&nbsp;Martin J. Hug ,&nbsp;Sara Tucci","doi":"10.1016/j.bbalip.2024.159582","DOIUrl":"10.1016/j.bbalip.2024.159582","url":null,"abstract":"","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159582"},"PeriodicalIF":3.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706392","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":"Role of USF1 in activating CYBA transcription and influencing NADPH-ROS-mediated oxidative stress and lipid accumulation in non-alcoholic fatty liver disease","authors":"Shaohua Zhuang ,&nbsp;Jinjin Fu ,&nbsp;Liwei Wu ,&nbsp;Xuanfu Xu ,&nbsp;Chuanyong Guo","doi":"10.1016/j.bbalip.2024.159581","DOIUrl":"10.1016/j.bbalip.2024.159581","url":null,"abstract":"<div><div>Nonalcoholic fatty liver disease (NAFLD) progression is relevant to oxidative stress, while NADPH oxidase can produce ROS. This study explored how the upstream stimulatory factor 1 (USF1) regulates cytochrome <em>b</em>-245 alpha chain (CYBA) expression through the NADPH-ROS pathway and its impact on oxidative stress and lipid accumulation in NAFLD. Bioinformatics analysis identified CYBA as a gene with altered expression in NAFLD. Mouse and cell models of NAFLD were established through high-fat diet (HFD) and palmitic acid (PA) treatment respectively. CYBA and USF1 expression was modulated using RNA interference, and their effects on NAFLD progression were then examined. ChIP and dual-luciferase reporter assays were performed to confirm the transcriptional regulation of CYBA by USF1. Elevated CYBA expression was observed in NAFLD. Reduced NADPH oxidase activity, oxidative stress, lipid accumulation, and inflammation were observed in NAFLD models after knocking down CYBA. USF1 was found to bind to the CYBA promoter and activate its transcription. Similar effects as CYBA knockdown on NAFLD were achieved by knocking down USF1. The protective impacts of USF1 silencing on NAFLD were reversed by overexpressing CYBA. In summary, this study demonstrates that USF1 mediates the transcriptional activation of CYBA, increasing NADPH-ROS-derived oxidative stress and lipid accumulation in NAFLD.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159581"},"PeriodicalIF":3.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692594","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":"RBM15 promotes lipogenesis and malignancy in gastric cancer by regulating N6-Methyladenosine modification of ACLY mRNA in an IGF2BP2-dependent manner","authors":"Xianlei Cai ,&nbsp;Xueying Li ,&nbsp;Miaozun Zhang ,&nbsp;Zhebin Dong ,&nbsp;Yihui Weng ,&nbsp;Weiming Yu","doi":"10.1016/j.bbalip.2024.159580","DOIUrl":"10.1016/j.bbalip.2024.159580","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) and lipid metabolism reprogramming play pivotal roles in cancer development. Nevertheless, the precise functions of m⁶A methyltransferase RNA Binding Motif Protein 15 (RBM15) and its interactions with ATP Citrate Lyase (ACLY) in gastric cancer (GC) have not been fully elucidated. In this study, we comprehensively investigate the biological roles and potential mechanisms of RBM15 and ACLY in GC. We employed a combination of fundamental experiments and bioinformatics analyses to unravel the enigmatic roles of RBM15 and ACLY. The expression of RBM15 was evaluated. The biological roles of RBM15 in GC cells were investigated through <em>in vitro</em> and <em>in vivo</em> studies. ACLY was selected as the candidate target of RBM15. Subsequently, to decipher the underlying mechanisms of the RBM15/ACLY axis, we conducted a series of experiments including methylated RNA immunoprecipitation qPCR, dual-luciferase reporter assays, and RNA immunoprecipitation qPCR. We observed a conspicuous upregulation of RBM15 in GC, and its heightened expression was associated with an unfavorable prognosis. Functionally, RBM15 fostered the proliferation and invasiveness of GC cells both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, ACLY emerged as the downstream target of RBM15 and it was validated as an oncogene in GC cells. RBM15 mediated the activation of ACLY by regulating m6A modification in an IGF2BP2-dependent manner, thereby driving lipogenesis and exacerbating the malignant characteristics in GC. The activation of ACLY, facilitated by RBM15/IGF2BP2-mediated m6A modification, drives lipogenesis and promotes the progression of GC.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159580"},"PeriodicalIF":3.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643835","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":"Inducible global knockout of surfeit locus protein 4 in adult mice results in hypolipidemia, intestinal lipid accumulation, liver injury, and increased mortality","authors":"Wei Chen ,&nbsp;Yuan Chen ,&nbsp;Baoye Song ,&nbsp;Lei Zhai ,&nbsp;Geru Tao ,&nbsp;Bingxiang Wang ,&nbsp;Boyan Liu ,&nbsp;Hao Wang ,&nbsp;Cindy X. Zhang ,&nbsp;Hong-mei Gu ,&nbsp;Deling Yin ,&nbsp;Shucun Qin ,&nbsp;Da-wei Zhang","doi":"10.1016/j.bbalip.2024.159577","DOIUrl":"10.1016/j.bbalip.2024.159577","url":null,"abstract":"<div><div>Surfeit locus protein 4 (SURF4) acts as a cargo receptor to mediate endoplasmic reticulum export of various cargos. We have shown that SURF4 is essential for secretion of hepatic very low-density lipoprotein and intestinal chylomicron. Knockdown of hepatic <em>Surf4</em> also significantly reduces the development of atherosclerosis and liver fibrosis without causing overt liver damage. However, constitutive global <em>Surf4</em> knockout results in embryonic lethality. To further understand the physiological role of SURF4, we generated tamoxifen-inducible global <em>Surf4</em> knockout mice. We found that conditional knockout of <em>Surf4</em> in adult mice (<em>Surf4</em>^ig-ko) significantly reduced mouse body weight. Male and female <em>Surf4</em>^ig-ko mice died approximately 30 and 50 days after tamoxifen administration, respectively. Triglyceride secretion and serum levels of total cholesterol, triglycerides, free fatty acids, apolipoprotein B-100, and apolipoprotein B-48 were significantly reduced in <em>Surf4</em>^ig-ko mice compared with <em>Surf4</em>^flox mice. Proteomics analysis of mouse serum samples revealed 308 proteins with significantly altered expression in <em>Surf4</em>^ig-ko mice that have unique functions and are involved in various biological processes. In addition, <em>Surf4</em>^ig-ko mice exhibited lipid accumulation in the intestine but not in the liver. However, in <em>Surf4</em>^ig-ko mice, liver weight was significantly reduced, and serum transaminase activity was significantly increased, indicating liver damage. Therefore, SURF4 is essential for survival in adult mice, suggesting that the therapeutic use of SURF4 requires precise tissue/cell type-specific targeting.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159577"},"PeriodicalIF":3.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643834","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":"Induction of ectosome formation by binding of phospholipases D from Loxosceles venoms to endothelial cell surface: Mechanism of interaction","authors":"Hanna Câmara da Justa ,&nbsp;Antonielle Beatriz Baldissera ,&nbsp;Mariana Izabele Machado ,&nbsp;Samira Hajjar Souza ,&nbsp;Nayanne Louise Costacurta Polli ,&nbsp;Marianna Boia-Ferreira ,&nbsp;Pedro Henrique de Caires Schluga ,&nbsp;Lucelia Donatti ,&nbsp;Ana Carolina M. Wille ,&nbsp;João Carlos Minozzo ,&nbsp;Luiza Helena Gremski ,&nbsp;Silvio S. Veiga","doi":"10.1016/j.bbalip.2024.159579","DOIUrl":"10.1016/j.bbalip.2024.159579","url":null,"abstract":"<div><div>Members of the phospholipase D (PLD) superfamily found in <em>Loxosceles</em> spider venoms are potent toxins with inflammatory and necrotizing activities. They degrade phospholipids in cell membranes, generating bioactive molecules that activate skin cells. These skin cells, in turn, activate leukocytes involved in dermonecrosis, characterized by aseptic coagulative necrosis. Although the literature has advanced in understanding the structure-function relationship, the cell biology resulting from the interactions of these molecules with cells remains poorly understood. In this study, we show that different cells exposed to recombinant PLDs bind these molecules to their plasma membrane, leading to the subsequent organization of extracellular microvesicles/ectosomes. The binding occurs as quickly as five minutes or less after exposure, increases over time, and eventually, the PLDs are expelled from the cell surface without generating cytotoxicity. PLDs are not endocytosed, nor do they spatially colocalize with acidic organelles in the intracellular environment. At least two regions of PLDs – the domain involved in magnesium ion coordination and the choline binding site – appear to play a role in cell surface binding and ectosome organization. However, the amino acids involved in catalysis do not participate in these events. The binding of these PLDs to the cell membrane, independent of catalytic activity, is sufficient to trigger intracellular signaling and enhance the expression of the pro-inflammatory IL-8 gene. These results are supported by the observation that isoforms of PLDs lacking catalytic activity induce an inflammatory response <em>in vivo</em> when injected into the skin of rabbits, without causing dermonecrosis. Our data indicate that these PLDs bind to the surface of target cells, promoting the organization of extracellular vesicles/ectosomes. Subsequently, these events activate pro-inflammatory genes and induce an inflammatory response <em>in vivo</em>. The binding to cells is not dependent on amino acids involved in catalysis but rather on amino acids involved in magnesium coordination. The binding of PLDs to the cell surface, formation of ectosomes, and activation of cells appear to initiate signals involved in inflammatory responses that can lead to dermonecrosis in accidents. This correlation is supported by experimental observations indicating that the events of toxin binding to cells, formation of microvesicles, and inflammatory responses observed both <em>in vitro</em> and <em>in vivo</em> are interconnected.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159579"},"PeriodicalIF":3.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638333","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":"Cholesterol metabolism in pancreatic cancer and associated therapeutic strategies","authors":"Tasvi Daya,&nbsp;Andrea Breytenbach,&nbsp;Liang Gu,&nbsp;Mandeep Kaur","doi":"10.1016/j.bbalip.2024.159578","DOIUrl":"10.1016/j.bbalip.2024.159578","url":null,"abstract":"<div><div>Pancreatic cancer remains one of the most lethal cancers due to late diagnosis and high chemoresistance. Despite recent progression in the development of chemotherapies, immunotherapies, and potential nanoparticles-based approaches, the success rate of therapeutic response is limited which is further compounded by cancer drug resistance. Understanding of emerging biological and molecular pathways causative of pancreatic cancer's aggressive and chemoresistance is vital to improve the effectiveness of existing therapeutics and to develop new therapies. One such under-investigated and relatively less explored area of research is documenting the effect that lipids, specifically cholesterol, and its metabolism, impose on pancreatic cancer. Dysregulated cholesterol metabolism has a profound role in supporting cellular proliferation, survival, and promoting chemoresistance and this has been well established in various other cancers. Thus, we aimed to provide an in-depth review focusing on the significance of cholesterol metabolism in pancreatic cancer and relevant genes at play, molecular processes contributing to cellular cholesterol homeostasis, and current research efforts to develop new cholesterol-targeting therapeutics. We highlight the caveats, weigh in different experimental therapeutic strategies, and provide possible suggestions for future research highlighting cholesterol's importance as a therapeutic target against pancreatic cancer resistance and cancer progression.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 2","pages":"Article 159578"},"PeriodicalIF":3.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614034","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":"How the liver transcriptome and lipid composition influence the progression of nonalcoholic fatty liver disease to hepatocellular carcinoma in a murine model","authors":"Marvin Leopold ,&nbsp;Paola Berenice Mass-Sanchez ,&nbsp;Marinela Krizanac ,&nbsp;Paula Štancl ,&nbsp;Rosa Karlić ,&nbsp;Patricia Prabutzki ,&nbsp;Victoria Parafianczuk ,&nbsp;Jürgen Schiller ,&nbsp;Anastasia Asimakopoulos ,&nbsp;Kathrin M. Engel ,&nbsp;Ralf Weiskirchen","doi":"10.1016/j.bbalip.2024.159574","DOIUrl":"10.1016/j.bbalip.2024.159574","url":null,"abstract":"<div><div>The incidence of nonalcoholic fatty liver disease (NAFLD) has been steadily increasing in Western society in recent years and has been recognized as a risk factor for the development of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the progression from NAFLD to HCC are still unclear, despite the use of suitable mouse models. To identify the transcriptional and lipid profiles of livers from mice with NAFLD-HCC, we induced both NAFLD and NAFLD-HCC pathologies in C57BL/6J mice and performed RNA-sequencing (RNA-seq) and targeted lipidomic analysis. Our RNA-seq analysis revealed that the transcriptional signature of NAFLD in mice is characterized by changes in inflammatory response and fatty acid metabolism. Moreover, the signature of NAFLD-HCC is characterized by processes typically observed in cancer, such as epithelial to mesenchymal transition, angiogenesis and inflammatory responses. Furthermore, we found that the diet used in this study inhibited cholesterol synthesis in both models. The analysis of lipid composition also showed a significant impact of the provided diet. Therefore, our study supports the idea that a Western diet (WD) affects metabolic processes and hepatic lipid composition. Additionally, the combination of a WD with the administration of a carcinogen drives the progression from NAFLD to HCC.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159574"},"PeriodicalIF":3.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603105","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":"RNA sequencing analysis reveals distinct gene expression patterns in infrapatellar fat pads of patients with end-stage osteoarthritis or rheumatoid arthritis","authors":"Anne-Mari Mustonen ,&nbsp;Marjo Malinen ,&nbsp;Ville Paakinaho ,&nbsp;Petri Lehenkari ,&nbsp;Sanna Palosaari ,&nbsp;Vesa Kärjä ,&nbsp;Petteri Nieminen","doi":"10.1016/j.bbalip.2024.159576","DOIUrl":"10.1016/j.bbalip.2024.159576","url":null,"abstract":"<div><div>Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases that share partly similar symptoms but have different, inadequately understood pathogeneses. Adipose tissues, including intra-articular infrapatellar fat pad (IFP), may contribute to their development. Analysis of differentially expressed genes (DEGs) in IFPs could improve the diagnostics of these conditions and help to develop novel treatment strategies. The aim was to identify potentially crucial genes and pathways discriminating OA and RA IFPs using RNA sequencing analysis. We aimed to distinguish genetically distinct patient groups as a starting point for further translational studies with the eventual goal of personalized medicine. Samples were collected from arthritic knees during total knee arthroplasty of sex- and age-matched OA and seropositive RA patients (<em>n</em> = 5–6/group). Metabolic pathways of interest were investigated by whole transcriptome sequencing, and DEGs were analyzed with univariate tests, hierarchical clustering (HC), and pathway analyses. There was significant interindividual variation in mRNA expression patterns, but distinct subgroups of OA and RA patients emerged that reacted similarly to their disease states based on HC. Compared to OA, RA samples showed 703 genes to be upregulated and 691 genes to be downregulated. Signaling pathway analyses indicated that these DEGs had common pathways in lipid metabolism, fatty acid biosynthesis and degradation, adipocytokine and insulin signaling, inflammatory response, and extracellular matrix organization. The divergent mRNA expression profiles in RA and OA suggest contribution of IFP to the regulation of synovial inflammatory processes and articular cartilage degradation and could provide novel diagnostic and therapeutic targets.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159576"},"PeriodicalIF":3.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567655","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}