Journal of physiology and biochemistry最新文献

{"title":"MicroRNA-enriched exosome as dazzling dancer between cancer and immune cells.","authors":"Chou-Yi Hsu, Abdulrahman T Ahmed, Pooja Bansal, Ahmed Hjazi, Hussein Riyadh Abdul Kareem Al-Hetty, Maytham T Qasim, Ibrokhim Sapaev, Mahamedha Deorari, Yasser Fakri Mustafa, Ahmed Elawady","doi":"10.1007/s13105-024-01050-x","DOIUrl":"https://doi.org/10.1007/s13105-024-01050-x","url":null,"abstract":"<p><p>Exosomes are widely recognized for their roles in numerous biological processes and as intercellular communication mediators. Human cancerous and normal cells can both produce massive amounts of exosomes. They are extensively dispersed in tumor-modeling animals' pleural effusions, ascites, and plasma from people with cancer. Tumor cells interact with host cells by releasing exosomes, which allow them to interchange various biological components. Tumor growth, invasion, metastasis, and even tumorigenesis can all be facilitated by this delicate and complex system by modifying the nearby and remote surroundings. Due to the existence of significant levels of biomolecules like microRNA, exosomes can modulate the immune system's stimulation or repression, which in turn controls tumor growth. However, the role of microRNA in exosome-mediated communication between immunological and cancer cells is still poorly understood. This study aims to get the most recent information on the \"yin and yang\" of exosomal microRNA in the regulation of tumor immunity and immunotherapy, which will aid current cancer treatment and diagnostic techniques.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased expression of IL-1β in adipose tissue in obesity influences the development of colon cancer by promoting inflammation.","authors":"Gabriela Neira, Javier Gómez-Ambrosi, Javier A Cienfuegos, Beatriz Ramírez, Sara Becerril, Amaia Rodríguez, María A Burrell, Jorge Baixauli, Amaia Mentxaka, Marcos Casado, Camilo Silva, Javier Escalada, Gema Frühbeck, Victoria Catalán","doi":"10.1007/s13105-024-01048-5","DOIUrl":"https://doi.org/10.1007/s13105-024-01048-5","url":null,"abstract":"<p><p>Excess adiposity contributes to the development of colon carcinoma (CC). Interleukin (IL)-1β is a pro-inflammatory cytokine relevant in obesity-associated chronic inflammation and tumorigenic processes. We herein aimed to study how obesity and CC affects the expression of IL1B, and to determine the impact of IL-1β on the regulation of metabolic inflammation and gut barrier function in the context of obesity and CC. Samples from 71 volunteers were used in a case-control study and a rat model of diet-induced obesity (DIO). Furthermore, bariatric surgery was used to determine the effect of weight loss on the intestinal gene expression levels of Il1b. To evaluate the effect of IL-1β and obesity in CC, we treated the adenocarcinoma cell line HT-29 with IL-1β and the adipocyte-conditioned medium (ACM) from patients with obesity. We showed that obesity (P < 0.05) and CC (P < 0.01) upregulated the transcript levels of IL1B in visceral adipose tissue as well as in the colon from patients with CC (P < 0.01). The increased expression of Il1b in the ileum and colon in DIO rats decreased after weight loss achieved by either sleeve gastrectomy or caloric restriction (both P < 0.05). ACM treatment on HT-29 cells upregulated (P < 0.05) the transcripts of IL1B and CCL2, while reducing (P < 0.05) the expression of the anti-inflammatory ADIPOQ and MUC2 genes. Additionally, IL-1β upregulated (P < 0.01) the expression of CCL2 and TNF whilst downregulating (P < 0.01) the transcript levels of IL4, ADIPOQ and TJP1 in HT-29 cells. We provide evidence of the important role of IL-1β in obesity-associated CC by directly promoting inflammation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive in silico CpG methylation analysis in hepatocellular carcinoma identifies tissue- and tumor-type specific marks disconnected from gene expression.","authors":"Idoia Bilbao, Miriam Recalde, Fabrice Daian, José Maria Herranz, María Elizalde, Mercedes Iñarrairaegui, Matteo Canale, Maite G Fernández-Barrena, Andrea Casadei-Gardini, Bruno Sangro, Matías A Ávila, Manuel F Landecho Acha, Carmen Berasain, María Arechederra","doi":"10.1007/s13105-024-01045-8","DOIUrl":"https://doi.org/10.1007/s13105-024-01045-8","url":null,"abstract":"<p><p>DNA methylation is crucial for chromatin structure, transcription regulation and genome stability, defining cellular identity. Aberrant hypermethylation of CpG-rich regions is common in cancer, influencing gene expression. However, the specific contributions of individual epigenetic modifications to tumorigenesis remain under investigation. In hepatocellular carcinoma (HCC), DNA methylation alterations are documented as in other tumor types. We aimed to identify hypermethylated CpGs in HCC, assess their specificity across other tumor types, and investigate their impact on gene expression. To this end, public methylomes from HCC, other liver diseases, and 27 tumor types as well as expression data from TCGA-LIHC and GTEx were analyzed. This study identified 39 CpG sites that were hypermethylated in HCC compared to control liver tissue, and were located within promoter, gene bodies, and intergenic CpG islands. Notably, these CpGs were predominantly unmethylated in healthy liver tissue and other normal tissues. Comparative analysis with 27 other tumors revealed both common and HCC-specific hypermethylated CpGs. Interestingly, the HCC-hypermethylated genes showed minimal expression in the different healthy tissues, with marginal changes in the level of expression in the corresponding tumors. These findings confirm previous evidence on the limited influence of DNA hypermethylation on gene expression regulation in cancer. It also highlights the existence of mechanisms that allow the selection of tissue-specific methylation marks in normally unexpressed genes during carcinogenesis. Overall, our study contributes to demonstrate the complexity of cancer epigenetics, emphasizing the need of better understanding the interplay between DNA methylation, gene expression dynamics, and tumorigenesis.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitic acid causes hepatocyte inflammation by suppressing the BMAL1-NAD+-SIRT2 axis","authors":"Savera Aggarwal, Archana Rastogi, Rakhi Maiwall, Jayesh K Sevak, Vipin Yadav, Jaswinder Maras, Sherin Sarah Thomas, Pratibha R Kale, Viniyendra Pamecha, Nagarajan Perumal, Nirupama Trehanpati, Gayatri Ramakrishna","doi":"10.1007/s13105-024-01042-x","DOIUrl":"https://doi.org/10.1007/s13105-024-01042-x","url":null,"abstract":"<p>Palmitic acid is the most abundant saturated fatty acid in circulation and causes hepatocyte toxicity and inflammation. As saturated fatty acid can also disrupt the circadian rhythm, the present work evaluated the connection between clock genes and NAD+ dependent Sirtuins in protecting hepatocytes from lipid-induced damage. Hepatocytes (immortal cells PH5CH8, hepatoma cells HepG2) treated with higher doses of palmitic acid (400-600μM) showed typical features of steatosis accompanied with growth inhibition and increased level of inflammatory markers (IL-6 IL-8, IL-1α and IL-1β) together with decline in NAD+ levels. Palmitic acid treated hepatocytes showed significant decline in not only the protein levels of SIRT2 but also its activity as revealed by the acetylation status of its downstream targets (Tubulin and NF-ƙB). Additionally, the circadian expression of both SIRT2 and BMAL1 was inhibited in presence of palmitic acid in only the non-cancerous hepatocytes, PH5CH8 cells. Clinical specimens obtained from subjects with NASH-associated fibrosis, ranging from absent (F0) to cirrhosis (F4), showed a significant decline in levels of SIRT2 and BMAL1, especially in the cirrhotic liver. Ectopic expression of BMAL1 or activating SIRT2 by supplementation with nicotinamide riboside (precursor of NAD+) dampened the palmitic acid induced lipoinflammation and lipotoxicity more effectively in PH5CH8 cells as compared to HepG2 cells. Mechanistically, palmitic acid caused transcriptional suppression of SIRT2 by disrupting the chromatin occupancy of BMAL1 at its promoter site. Overall, the work suggested that SIRT2 is a clock-controlled gene that is transcriptionally regulated by BMAL1. In conclusion the activation of the BMAL1-NAD+-SIRT2 axis shows hepatoprotective effects by preventing lipotoxicity and dampening inflammation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"193 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Irisin in exercise training-regulated endoplasmic reticulum stress, autophagy and myogenesis in the skeletal muscle after myocardial infarction","authors":"Shou Pan, Wujing Ren, Yifang Zhao, Mengxin Cai, Zhenjun Tian","doi":"10.1007/s13105-024-01049-4","DOIUrl":"https://doi.org/10.1007/s13105-024-01049-4","url":null,"abstract":"<p>Patients with heart failure (HF) are often accompanied by skeletal muscle abnormalities, which can lead to exercise intolerance and compromise daily activities. Irisin, an exercise training (ET) -induced myokine, regulates energy metabolism and skeletal muscle homeostasis. However, the precise role of Irisin in the benefits of ET on inhibiting skeletal muscle atrophy, particularly on endoplasmic reticulum (ER) stress, autophagy, and myogenesis following myocardial infarction (MI) remains unclear. In this study, we investigated the expression of Irisin protein in wild-type mice with MI, and assessed its role in the beneficial effects of ET using an <i>Fndc5</i> knockout mice. Our findings revealed that MI reduced muscle fiber cross-sectional area (CSA), while downregulating the expression of Irisin, PGC-1α and SOD1. Concurrently, MI elevated the levels of ER stress and apoptosis, and inhibited autophagy in skeletal muscle. Conversely, ET mitigated ER stress and apoptosis in the skeletal muscle of infarcted mice. Notably, <i>Fndc5</i> knockout worsened MI-induced ER stress and apoptosis, suppressed autophagy and myogenesis, and abrogated the beneficial effects of ET. In conclusion, our findings highlight the role of Irisin in the ET-mediated alleviation of skeletal muscle abnormalities. This study provides valuable insights into MI-induced muscle abnormalities and enhances our understanding of exercise rehabilitation mechanisms in clinical MI patients.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"19 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT1 and FOXO1 role on MASLD risk: effects of DHA-rich n-3 PUFA supplementation and exercise in aged obese female mice and in post-menopausal overweight/obese women","authors":"Jinchunzi Yang, Elisa Félix-Soriano, Alejandro Martínez-Gayo, Javier Ibañez-Santos, Neira Sáinz, J Alfredo Martínez, María J. Moreno-Aliaga","doi":"10.1007/s13105-024-01044-9","DOIUrl":"https://doi.org/10.1007/s13105-024-01044-9","url":null,"abstract":"<p>Sirtuins 1 (SIRT1) and Forkhead box protein O1 (FOXO1) expression have been associated with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Exercise and/or docosahexaenoic acid (DHA) supplementation have shown beneficial effects on MASLD. The current study aims to assess the relationships between <i>Sirt1</i>, <i>Foxo1</i> mRNA levels and several MASLD biomarkers, as well as the effects of DHA-rich n-3 PUFA supplementation and/or exercise in the steatotic liver of aged obese female mice, and in peripheral blood mononuclear cells (PBMCs) of postmenopausal women with overweight/obesity. In the liver of 18-month-old mice, <i>Sirt1</i> levels positively correlated with the expression of genes related to fatty acid oxidation, and negatively correlated with lipogenic and proinflammatory genes. Exercise (long-term treadmill training), especially when combined with DHA, upregulated hepatic <i>Sirt1</i> mRNA levels. Liver <i>Foxo1</i> mRNA levels positively associated with hepatic triglycerides (TG) content and the expression of lipogenic and pro-inflammatory genes, while negatively correlated with the lipolytic gene <i>Hsl</i>. In PBMCs of postmenopausal women with overweight/obesity, <i>FOXO1</i> mRNA expression negatively correlated with the hepatic steatosis index (HSI) and the Zhejiang University index (ZJU). After 16-weeks of DHA-rich PUFA supplementation and/or progressive resistance training (RT), most groups exhibited reduced MASLD biomarkers and risk indexes accompanying with body fat mass reduction, but no significant changes were found between the intervention groups. However, in PBMCs n-3 supplementation upregulated <i>FOXO1</i> expression, and the RT groups exhibited higher <i>SIRT1</i> expression. In summary, SIRT1 and FOXO1 could be involved in the beneficial mechanisms of exercise and n-3 PUFA supplementation related to MASLD manifestation.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":"105 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary-Based Diabetes Risk Score and breast cancer: a prospective evaluation in the SUN project.","authors":"Inmaculada Aguilera-Buenosvinos, Miguel A Martínez-González, Andrea Romanos-Nanclares, Rodrigo Sánchez-Bayona, Carlos E de Andrea, Ligia J Domínguez, Estefania Toledo","doi":"10.1007/s13105-024-01036-9","DOIUrl":"https://doi.org/10.1007/s13105-024-01036-9","url":null,"abstract":"<p><p>An association between type 2 diabetes (T2D) and breast cancer risk has been reported. This association can be potentially explained by alteration of the insulin/IGF system. Therefore, we aimed to prospectively investigate whether a previously reported Dietary-Based Diabetes Risk Score (DDS) inversely associated with T2D was also associated with breast cancer risk in the SUN (\"Seguimiento Universidad de Navarra\") cohort. We followed up 10,810 women (mean age = 35 years, SD = 11 years) for an average of 12.5 years during which 147 new cases of invasive breast cancer were diagnosed. A validated 136-item FFQ was administered at baseline and after 10 years of follow-up. The DDS (range: 11 to 55 points) positively weighted vegetables, fruit, whole cereals, nuts, coffee, low-fat dairy, fiber, PUFA; while it negatively weighted red meat, processed meats, and sugar-sweetened beverages. The DDS was categorized into tertiles. Self-reported medically diagnosed breast cancer cases were confirmed through medical records. We found a significant inverse association between the intermediate tertile of the DDS score and overall breast cancer risk (Hazard ratio, HR_{T2 vs. T1}= 0.55; 95% CI: 0.36-0.82) and premenopausal breast cancer risk (HR_T2= 0.26; 95% CI: 0.13-0.53), but not for the highest tertile. This association was stronger among women with a BMI < 25 kg/m² (p_interaction: 0.029). In conclusion, moderate adherence to the DDS score was associated with a lower risk of breast cancer, especially among premenopausal women and women with a lower BMI. These findings underscore the importance of antidiabetic diet in reducing the risk of breast cancer.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle-enriched microRNA-486-mediated regulation of muscular atrophy and exercise.","authors":"Dayong Qiu, Yan Zhang, Pinshi Ni, Zhuangzhi Wang, Luodan Yang, Fanghui Li","doi":"10.1007/s13105-024-01043-w","DOIUrl":"https://doi.org/10.1007/s13105-024-01043-w","url":null,"abstract":"<p><p>The objectives of this review were to understand the impact of microRNA-486 on myogenesis and muscle atrophy, and the change of microRNA-486 following exercise, and provide valuable information for improving muscle atrophy based on exercise intervention targeting microRNA-486. Muscle-enriched microRNAs (miRNAs), also referred to as myomiRs, control various processes in skeletal muscles, from myogenesis and muscle homeostasis to different responses to environmental stimuli such as exercise. MicroRNA-486 is a miRNA in which a stem-loop sequence is embedded within the ANKYRIN1 (ANK1) locus and is strictly conserved across mammals. MicroRNA-486 is involved in the development of muscle atrophy caused by aging, immobility, prolonged exposure to microgravity, or muscular and neuromuscular disorders. PI3K/AKT signaling is a positive pathway, as it increases muscle mass by increasing protein synthesis and decreasing protein degradation. MicroRNA-486 can activate this pathway by inhibiting phosphatase and tensin homolog (PTEN), it may also indirectly inhibit the HIPPO signaling pathway to promote cell growth. Exercises regulate microRNA-486 expression both in blood and muscle. This review focused on the recent elucidation of sarcopenia regulation by microRNA-486 and its effects on pathological states, including primary muscular disease, secondary muscular disorders, and age-related sarcopenia. Additionally, the role of exercise in regulating skeletal muscle-enriched microRNA-486 was highlighted, along with its physiological significance. Growing evidence indicates that microRNA-486 significantly impacts the development of muscle atrophy. MicroRNA-486 has great potential to become a therapeutic target for improving muscle atrophy through exercise intervention.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibin subunit beta B (INHBB): an emerging role in tumor progression.","authors":"Ying Liu, Qing Zhou, Guoying Zou, Wenling Zhang","doi":"10.1007/s13105-024-01041-y","DOIUrl":"https://doi.org/10.1007/s13105-024-01041-y","url":null,"abstract":"<p><p>The gene inhibin subunit beta B (INHBB) encodes the inhibin βB subunit, which is involved in forming protein members of the transforming growth factor-β (TGF-β) superfamily. The TGF-β superfamily is extensively involved in cell proliferation, differentiation, adhesion, movement, metabolism, communication, and death. Activins and inhibins, which belong to the TGF-β superfamily, were first discovered in ovarian follicular fluid. They were initially described as regulators of pituitary follicle-stimulating hormone (FSH) secretion both in vivo and in vitro. Later studies found that INHBB is expressed not only in reproductive organs such as the ovary, uterus, and testis but also in numerous other organs, including the brain, spinal cord, liver, kidneys, and adrenal glands. This wide distribution implies its involvement in the normal physiological functions of various organs; however, the mechanisms underlying these functions have not yet been fully elucidated. Recent studies suggest that INHBB plays a significant, yet complex role in tumorigenesis. It appears to have dual effects, promoting tumor progression in some contexts while inhibiting it in others, although these roles are not yet fully understood. In this paper, we review the different expression patterns, functions, and mechanisms of INHBB in normal and tumor tissues to illustrate the research prospects of INHBB in tumor progression.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sphingosine 1-phosphate protective effect on human proximal tubule cells submitted to an in vitro ischemia model: the role of JAK2/STAT3.","authors":"Juliane Lopes de Assis, Gloria Maria Ramalho Soares Grelle, Aline Marie Fernandes, Bárbara da Silva Aniceto, Pedro Pompeu, Fabiana Vieira de Mello, Rafael Garrett, Rafael Hospodar Felippe Valverde, Marcelo Einicker-Lamas","doi":"10.1007/s13105-024-01038-7","DOIUrl":"https://doi.org/10.1007/s13105-024-01038-7","url":null,"abstract":"<p><p>Acute kidney injury is a serious public health problem worldwide, being ischemia and reperfusion (I/R) the main lesion-aggravating factor that contributes to the evolution towards chronic kidney disease. Nonetheless, intervention approaches currently available are just considered palliative options. In order to offer an alternative treatment, it is important to understand key factors involved in the development of the disease including the rescue of the affected cells and/or the release of paracrine factors that are crucial for tissue repair. Bioactive lipids such as sphingosine 1-phosphate (S1P) have significant effects on the modulation of signaling pathways involved in tissue regeneration, such as cell survival, proliferation, differentiation, and migration. The main objective of this work was to explore the protective effect of S1P using human kidney proximal tubule cells submitted to a mimetic I/R lesion, via ATP depletion. We observed that the S1P pre-treatment increases cell survival by 50% and preserves the cell proliferation capacity of injured cells. We showed the presence of different bioactive lipids notably related to tissue repair but, more importantly, we noted that the pre-treatment with S1P attenuated the ischemia-induced effects in response to the injury, resulting in higher endogenous S1P production. All receptors but S1PR3 are present in these cells and the protective and proliferative effect of S1P/S1P receptors axis occur, at least in part, through the activation of the SAFE pathway. To our knowledge, this is the first time that S1PR4 and S1PR5 are referred in these cells and also the first indication of JAK2/STAT3 pathway involvement in S1P-mediated protection in an I/R renal model.</p>","PeriodicalId":16779,"journal":{"name":"Journal of physiology and biochemistry","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}