Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"The potential biological function of STARD8 in prostate cancer: A bioinformatic and experimental validation study","authors":"Zichuang Xu ,&nbsp;Xiaojian Chen ,&nbsp;Yeying He ,&nbsp;Jiaying Tong ,&nbsp;Chaoyue Chen ,&nbsp;Meiqing Ding ,&nbsp;Wei Chen ,&nbsp;Huiliang Zhou ,&nbsp;Xiaohui Zheng ,&nbsp;Yunbei Xiao","doi":"10.1016/j.bbadis.2025.167897","DOIUrl":"10.1016/j.bbadis.2025.167897","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is one of the most prevalent malignancies among men, with its incidence and mortality rates rising globally, posing a significant threat to men's health. STARD8, an emerging tumor suppressor gene, has been reported to inhibit cancer cell proliferation and migration in certain cancers. However, its role in PCa remains inadequately understood.</div></div><div><h3>Methods</h3><div>Bioinformatic analyses utilizing the TCGA, GTEx, and MSigDB databases were conducted to investigate the biological functions of STARD8. Differential expression of STARD8 was confirmed through immunohistochemistry, western blotting (WB), and quantitative PCR (Q-PCR) using clinical samples and cell lines. Functional assays, including STARD8 silencing and overexpression in PC3, DU145, C4-2B, LNCaP and WPMY-1 cells, were performed using immunofluorescence staining, WB, EdU assays, and comet assays.</div></div><div><h3>Results</h3><div>Transcriptomic data and clinical samples revealed that STARD8 expression is significantly reduced in PCa. In PCa cells, silencing STARD8 enhanced cell adhesion, migration, and invasion, whereas overexpression of STARD8 significantly suppressed these processes. Furthermore, STARD8 expression was found to be closely associated with immune evasion and drug sensitivity in PCa. Functional assays demonstrated that upregulation of STARD8 in PCa cells enhanced the chemotherapeutic efficacy of cisplatin. Mechanistically, STARD8 negatively regulated total FAK and p-FAK protein levels, thereby modulating PCa cell migration, proliferation, immune responses, and drug sensitivity.</div></div><div><h3>Conclusion</h3><div>This study identifies STARD8 as a critical tumor suppressor with significant roles in regulating cell proliferation, migration, immune evasion, and drug sensitivity in tumors.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167897"},"PeriodicalIF":4.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922825","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":"Tubular specific glutathione peroxidase 3 deletion exacerbates kidney damage in IRI-AKI mice","authors":"Jinrong He ,&nbsp;Xueqin Wu ,&nbsp;Jie Qiao ,&nbsp;Xian Xie ,&nbsp;Yu Wang ,&nbsp;Hao Zhang ,&nbsp;Wei Zhang","doi":"10.1016/j.bbadis.2025.167895","DOIUrl":"10.1016/j.bbadis.2025.167895","url":null,"abstract":"<div><div>Ischemia-reperfusion injury stands as a primary instigator of acute kidney injury (AKI), prominently driven by oxidative stress. Among the critical antioxidant defenses is glutathione peroxidase 3 (GPX3), an enzyme generated by renal tubular epithelial cells. Our prior investigations have unveiled a substantial downregulation of GPX3 in renal tissues gleaned from AKI patients and murine models. This study aims to investigate the role of tubular cell-specific <em>Gpx3</em> deletion on ischemia-reperfusion injury-induced AKI (IRI-AKI) in a murine model and delineate the potential underlying mechanisms.</div><div>By generating renal tubular epithelial cell-specific <em>Gpx3</em> knockout mice and inducing IRI-AKI, we assessed a spectrum of kidney injury indices including renal function, oxidative stress, apoptosis and mitochondrial dynamics. Additionally, we conducted transcriptome sequencing and bioinformatics analyses. The outcomes underscore that the deficiency of GPX3 in tubular cells exacerbates tubular injury, renal dysfunction, oxidative stress, apoptosis, and mitochondrial dynamic disturbances in the context of IRI-AKI. Sequencing and bioinformatics analysis suggest that the <em>Gpx3</em> deletion predominantly impacts pathways associated with metabolism and inflammation.</div><div>In conclusion, the tubular cell-specific deficiency of GPX3 exacerbates renal injury by intensifying oxidative stress, fostering mitochondrial impairment, perturbing metabolic processes and fueling inflammation. The targeted restoration of GPX3 in the renal tubular emerges as a potential therapeutic avenue for mitigating IRI-AKI.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167895"},"PeriodicalIF":4.2,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922824","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":"Exosomes generated from bone marrow mesenchymal stem cells limit the damage caused by myocardial ischemia-reperfusion via controlling the AMPK/PGC-1α signaling pathway","authors":"Yangping Zhuang ,&nbsp;Yu Wang ,&nbsp;Xiahong Tang ,&nbsp;Nan Zheng ,&nbsp;Shirong Lin ,&nbsp;Jun Ke ,&nbsp;Feng Chen","doi":"10.1016/j.bbadis.2025.167890","DOIUrl":"10.1016/j.bbadis.2025.167890","url":null,"abstract":"<div><div>Myocardial ischemia/reperfusion (I/R) injury is one of the problems after coronary artery recanalization in patients with acute myocardial infarction, and the discovery of exosomes presents a broad potential for treating myocardial I/R injury. This work examined the function and regulatory mechanisms of exosomes produced from bone marrow mesenchymal stem cells (BMSCs-Exo) in myocardial I/R injury. Rats with I/R injuries had their myocardium directly injected with BMSCs-Exo. The outcomes demonstrated that cardiac function was enhanced and BMSCs-Exo dramatically decreased myocardial infarct size. Transcriptome sequencing was performed on heart tissues from the model and exosome-treated groups. GO and KEGG enrichment analyses revealed that exosomes might mitigate myocardial I/R damage via the AMPK/PGC-1α signaling pathway, confirmed by both in vitro and in vivo tests. The findings imply that compound C and sh-AMPK reverse the activation of PGC-1α and its downstream proteins and negate the protective effects of exosomes against oxidative stress and mitochondrial function in damaged cardiomyocytes. On the other hand, p-AMPK expression was unaffected by PGC-1α silencing. It was demonstrated that via activating the AMPK/PGC-1α signaling pathway, BMSCs-Exo might reduce oxidative stress and mitochondrial dysfunction in cardiomyocytes, thereby protecting against myocardial I/R damage.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167890"},"PeriodicalIF":4.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906164","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":"Next-generation probiotics Alistipes onderdonkii enhances the efficacy of anti-PD-1 therapy in colorectal cancer","authors":"Jiaxuan Xin ,&nbsp;Yandong Xiang ,&nbsp;Juan Jiang ,&nbsp;Zhengqi Jiang ,&nbsp;Bo Yi","doi":"10.1016/j.bbadis.2025.167891","DOIUrl":"10.1016/j.bbadis.2025.167891","url":null,"abstract":"<div><div>Despite significant breakthroughs of therapeutic antibodies targeting PD-1 in cancer treatment, most colorectal cancer (CRC) patients respond poorly to anti-PD-1 immunotherapy. The combination therapy strategies are used to overcome the limitations mentioned above. <em>Alistipes</em> (<em>A.</em>) <em>onderdonkii</em> has anti-cancer effects. This study aimed to examine <em>A. onderdonkii'</em>s effects and the related mechanisms in the anti-PD-1 treatment for CRC. In this study, anti-PD-1 therapy notably affected gut microbiota community composition in mice, particularly upregulating <em>A. onderdonkii</em> abundance. <em>A. onderdonkii</em> supplementation markedly promoted anti-PD-1 therapy's effectiveness on CRC treatment, as manifested by the elevated CD8⁺ T cell infiltration, promoted intestinal barrier integrity, and affected serum metabolomics. <em>A. onderdonkii</em> showed similar effects to the identified next-generation probiotics (NGP) <em>Akkermansia</em> (<em>A.</em>) <em>muciniphila</em>. Additionally, the combination therapy of anti-PD-1 and probiotics supplementation reduced PD-1 level and elevated IL-2 level, indicating that anti-PD-1 combined with <em>A. onderdonkii</em> efficiently restored T cell functions by inhibiting suppressive checkpoints. In conclusion, anti-PD-1 plus <em>A. onderdonkii</em> supplementation could account for a potential method for CRC therapy. These results provide strong evidence for <em>A. onderdonkii</em> as a potential NGP.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167891"},"PeriodicalIF":4.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929401","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":"Engineering a three-dimensional liver steatosis model","authors":"Elizabeth K. Johnston ,&nbsp;Zhou Fang ,&nbsp;Alejandro Soto-Gutierrez ,&nbsp;C. Burcin Taner ,&nbsp;Keith E. Cook ,&nbsp;Liu Yang ,&nbsp;Rosalyn D. Abbott","doi":"10.1016/j.bbadis.2025.167888","DOIUrl":"10.1016/j.bbadis.2025.167888","url":null,"abstract":"<div><div>Liver transplantation is the key treatment for liver failure, yet organ scarcity, exacerbated by high discard rates of steatotic livers, leads to high waitlist mortality. Preclinical models of steatosis are necessary to understand the pathophysiology of the disease and to develop pharmacological interventions to decrease disease burden and liver discard rate. In this paper, we develop an expedited 3D steatotic organoid model containing primary human hepatocytes and non-parenchymal cells. We present our iterative approach as we transition from 2D to 3D models and from immortalized to primary cells to optimize conditions for the development of a 3D human steatosis model. Both primary cell aggregation and steatosis induction time were reduced from the standard, 5–7 days, to 2 days. Our 3D model incorporates human primary hepatocytes from discarded liver tissues, which have not been used in organoids previously due to their rapid loss of phenotype in culture. After optimizing our steatosis induction media there was a mix of macro- and micro-steatosis in these primary hepatocytes which is consistent with the human pathology. Our approach achieves a model reflective of the liver pathology, preserving cellular phenotypes and viability while exhibiting markers of oxidative stress, a key factor contributing to complications in the transplantation of steatotic livers.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167888"},"PeriodicalIF":4.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916523","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":"Down-regulating HDAC2-LTA4H pathway ameliorates renal ischemia-reperfusion injury","authors":"Kai Ye ,&nbsp;Jixuan Li ,&nbsp;Zhixiao Huo ,&nbsp;Jian Xu ,&nbsp;Qinghai Dai ,&nbsp;Kunyan Qiao ,&nbsp;Yu Cao ,&nbsp;Lihua Yan ,&nbsp;Wei Liu ,&nbsp;Yue Hu ,&nbsp;Liang Xu ,&nbsp;Rui Su ,&nbsp;Yu Zhu ,&nbsp;Yuqiang Mi","doi":"10.1016/j.bbadis.2025.167889","DOIUrl":"10.1016/j.bbadis.2025.167889","url":null,"abstract":"<div><h3>Background</h3><div>The activation of histone deacetylase 2 (HDAC2) is the main pathogenesis of acute kidney injury (AKI), one of the leading causes of end-stage kidney disease. However, the regulatory role of HDAC2 upregulation on inflammation in AKI is still unclear.</div></div><div><h3>Results</h3><div>In this study, we found that treatment with HDAC2 inhibitor BRD6688 could mitigate the degree of mesangial sclerosis, interstitial infiltration and tubular atrophy, reduce the concentration of blood urea nitrogen (BUN) and serum creatinine (Scr), improve the proliferation, anti-apoptotic, anti-oxidative stress and angiogenesis effects of renal cells. Our results mainly indicated that renal HDAC2 activity was increased by casein kinase 2 (CK2) in renal ischemia reperfusion (I/R) models, and HDAC2 genetic ablation in HREpiC cells suppressed the leukotriene B4 (LTB4) production. Renal leukotriene A4 hydrolase (LTA4H) activity was increased in AKI mice in a HDAC2-dependent manner. LTB4 could induce monocytes to differentiate into M1 macrophages, while BRD6688 could suppress this effect and force the M1 macrophages polarize to M2 macrophages.</div></div><div><h3>Conclusion</h3><div>Inhibition of HDAC2 activities by BRD6688 could suppress the progression of renal I/R injury through the regulation of LTA4H and macrophage polarization.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167889"},"PeriodicalIF":4.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916524","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":"Exploring the cognitive impacts of diabetic neuropathy: a comprehensive review","authors":"Maamoon Mian ,&nbsp;Farhood Salehi ,&nbsp;Rishi Patel ,&nbsp;Jihane Tahiri ,&nbsp;Adam Bel-Hadj-Kacem ,&nbsp;Ali Alhaque ,&nbsp;Ryan Eldin ,&nbsp;P. Hemachandra Reddy","doi":"10.1016/j.bbadis.2025.167892","DOIUrl":"10.1016/j.bbadis.2025.167892","url":null,"abstract":"<div><div>Diabetic neuropathy (DPN) is known to affect various aspects of health, including cognitive function. This study explores how DPN influences cognitive performance and examines the interplay between DPN, gender differences, Alzheimer's Disease (AD), and the socioeconomic burden of neuropathic pain. The research involved a comprehensive review and analysis of 55 studies focusing on cognitive function in diabetic patients with and without DPN. Various cognitive assessments, including memory, processing speed, and olfactory function, were used to evaluate cognitive performance. Gender differences were analyzed in the context of cognitive impairment and neuropathic pain. Additionally, the relationship between peripheral neuropathy and AD was investigated through measures of nerve conduction velocities and amyloid protein deposits. The impact of physical and psychological factors on neuropathic pain and cognitive function was also examined. The findings indicate that diabetic patients with DPN exhibit more severe cognitive impairments compared to those without DPN and healthy controls. Cognitive deficits were particularly notable in memory and processing speed. Gender differences revealed that women with DPN experience more pronounced cognitive dysfunction and a higher incidence of painful neuropathy compared to men. Analysis of peripheral nerve conduction velocities and amyloid deposits suggested a link between neuropathy and AD. Furthermore, poor glycemic control emerged as a critical factor affecting both neuropathy and cognitive function. Psychological distress and socioeconomic factors were found to significantly influence the management and outcomes of neuropathic pain. The study underscores the complex interaction between DPN and cognitive impairment, highlighting the importance of integrated diagnostic and therapeutic approaches. The pronounced cognitive deficits in women and the link between DPN and AD emphasize the need for gender-specific and multifaceted treatment strategies. The socioeconomic impact of neuropathic pain and the role of psychological factors in exacerbating pain and cognitive decline suggest that comprehensive management plans should address both physical and mental health aspects to improve overall patient outcomes.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167892"},"PeriodicalIF":4.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906163","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":"Generation and characterization of a chronic in vitro model to study the early stage of metabolic dysfunction-associated steatotic liver disease (MASLD)","authors":"Vandana Singh ,&nbsp;Partha Chattopadhyay ,&nbsp;Fabeha Fatima ,&nbsp;Praveen Singh ,&nbsp;Rajesh Pandey ,&nbsp;Anurag Agrawal ,&nbsp;Soumya Sinha Roy","doi":"10.1016/j.bbadis.2025.167886","DOIUrl":"10.1016/j.bbadis.2025.167886","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic and progressive liver disease with an increasing global burden that starts with an early stage of simple steatosis (MASL) which frequently progresses to liver cirrhosis and hepatocellular carcinoma (HCC). Despite its widespread occurrence, the MASL or steatotic stage, characterized by excessive fat accumulation in the liver and considered reversible and benign, has not been extensively studied. To study MASL effectively, it is imperative to have a clinically relevant model system that focuses solely on steatosis, in a progressive and time-dependent manner, recapitulating molecular changes associated with human disease. We established a chronic cellular model of MASL using a primary immortalized human hepatocyte cell line treated with a low dose mixture of fatty acids. This model mimics the pattern of chronic disease progression, shows minimal lipotoxicity, exhibits progressive lipid accumulation (from early to moderate steatosis), and demonstrates macrosteatosis, a hallmark of MASL. To determine whether this model recapitulates both morphological and molecular aspects of steatosis, we measured the expression of key genes and pathways found to be dysregulated in a recently available early MASL patient dataset as well as a non-human primate model of MASL. In support of the relevance of our model, we observed increased fatty acid uptake, lipogenesis, mitochondrial activity, metabolic rewiring, and autophagic alterations that significantly overlap with the pathological features of human and non-human primate MASL. In conclusion, we generate a relevant cellular model of steatosis that can serve as a robust platform for screening of existing chemical libraries to identify potent inhibitors of MASL as well as discovering novel therapeutic targets by mechanistically studying altered molecular signatures associating early stages of MASLD.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167886"},"PeriodicalIF":4.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916522","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":"Targeting enhanced mitochondrial respiration chain activity as a potential therapeutic approach for endometriosis","authors":"Katarína Kalinová ,&nbsp;Benjamin Gottschalk ,&nbsp;Martin Hirtl ,&nbsp;Julian Ostaku ,&nbsp;Sonja Gabrijelčič ,&nbsp;Alwin Sokolowski ,&nbsp;Ernst Malle ,&nbsp;Wolfgang F. Graier ,&nbsp;Corina T. Madreiter-Sokolowski","doi":"10.1016/j.bbadis.2025.167885","DOIUrl":"10.1016/j.bbadis.2025.167885","url":null,"abstract":"<div><div>Endometriosis is a chronic condition defined by the presence of endometrial-like tissue outside the uterus. Since endometriotic cells share similarities with cancer cells, including uncontrolled cell growth and invasion, we investigated whether cancer cell-specific rewiring of mitochondrial signaling is also present in endometriotic cells.</div><div>We utilized the endometriotic cell line 12Z and investigated its mitochondrial function in comparison with the uterine cancer cell line SK-UT-1 and the mammary epithelial cell line hTERT-HME1. We could show that the endometriotic 12Z cells share structural similarities with cancerous SK-UT-1 cells with enhanced colocalization between the endoplasmic reticulum and mitochondria and increased cristae width and density associated with facilitated mitochondrial Ca²⁺ uptake. However, an increase in the reduction equivalent yield and oxygen consumption rate was exclusively found in 12Z cells, whereas the reduced ΔΨ_m and the reverse mode of F_OF₁-ATP synthase were also detected in SK-UT-1 cells. These features rendered both cell types susceptible to quercetin and oligomycin A treatment.</div><div>We assume that the complexes of the electron transport chain and the F_OF₁-ATP synthase in reverse mode have a crucial role in maintaining mitochondrial membrane potential and, thereby, mitochondrial integrity of endometriotic 12Z cells. Therefore, targeting the electron transport chain or the reverse mode of F_OF₁-ATP synthase may represent a promising new treatment strategy for endometriosis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167885"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912161","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":"The role of FLVCR1 and FLVCR2 in choline transport in the Caco-2 intestinal epithelial cell model and rat small intestine","authors":"Tomoya Yasujima ,&nbsp;Chitaka Namba ,&nbsp;Yosuke Azuma ,&nbsp;Yutaro Shinoda ,&nbsp;Isamu Matake ,&nbsp;Mione Yamasaki ,&nbsp;Haruka Morimoto ,&nbsp;Mana Namai ,&nbsp;Hiroyuki Kusuhara ,&nbsp;Katsuhisa Inoue ,&nbsp;Takahiro Yamashiro ,&nbsp;Hiroaki Yuasa","doi":"10.1016/j.bbadis.2025.167883","DOIUrl":"10.1016/j.bbadis.2025.167883","url":null,"abstract":"<div><div>Choline is a vital cationic nutrient for maintaining organismal homeostasis, partially synthesized in the liver but primarily obtained from dietary sources. While previous studies have explored mechanisms of choline absorption in intestinal cells, the precise roles of specific transporters remain to be fully elucidated. This study aimed to investigate the roles of the choline transporters feline leukemia virus subgroup C receptor 1 (FLVCR1) and FLVCR2. Using MDCKII cells expressing human FLVCR1 or FLVCR2, the study revealed that FLVCR1 facilitates choline efflux from the basolateral membrane, while FLVCR2 enables choline uptake through the apical membrane. Functional analyses of FLVCR1 and FLVCR2 variants identified mutations that significantly reduce choline uptake activity. Knockdown experiments in Caco-2 cells resulted in significantly reduced cellular uptake of choline. Functional analysis of choline transport in the everted tissue sacs of the rat small intestine suggested that Flvcr2 aids intestinal choline uptake. Conclusively, the findings of this study indicate that FLVCR1 and FLVCR2 work cumulatively to regulate intestinal choline absorption. These findings provide novel insights into the roles of FLVCR1 and FLVCR2 and offer bases for further research into choline transport mechanisms in the small intestine.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 6","pages":"Article 167883"},"PeriodicalIF":4.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929400","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}