Experimental and Molecular Medicine最新文献

{"title":"NSCLC mechanobiology: Delving into the intricate pathways involved in the dynamic interplay between tumors and the TME","authors":"Kostas A. Papavassiliou, Antonios N. Gargalionis, Efthimia K. Basdra, Athanasios G. Papavassiliou","doi":"10.1038/s12276-024-01379-9","DOIUrl":"10.1038/s12276-024-01379-9","url":null,"abstract":"","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"281-282"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01379-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trogocytosis-mediated immune evasion in the tumor microenvironment","authors":"Jeonghyun Kim, Soyeon Park, Jungseo Kim, Yewon Kim, Hong Min Yoon, Bima Rexa Rayhan, Jaekwang Jeong, Alfred L. M. Bothwell, Jae Hun Shin","doi":"10.1038/s12276-024-01364-2","DOIUrl":"10.1038/s12276-024-01364-2","url":null,"abstract":"Trogocytosis is a dynamic cellular process characterized by the exchange of the plasma membrane and associated cytosol during cell-to-cell interactions. Unlike phagocytosis, this transfer maintains the surface localization of transferred membrane molecules. For example, CD4 T cells engaging with antigen-presenting cells undergo trogocytosis, which facilitates the transfer of antigen-loaded major histocompatibility complex (MHC) class II molecules from antigen-presenting cells to CD4 T cells. This transfer results in the formation of antigen-loaded MHC class II molecule-dressed CD4 T cells. These “dressed” CD4 T cells subsequently participate in antigen presentation to other CD4 T cells. Additionally, trogocytosis enables the acquisition of immune-regulatory molecules, such as CTLA-4 and Tim3, in recipient cells, thereby modulating their anti-tumor immunity. Concurrently, donor cells undergo plasma membrane loss, and substantial loss can trigger trogocytosis-mediated cell death, termed trogoptosis. This review aims to explore the trogocytosis-mediated transfer of immune regulatory molecules and their implications within the tumor microenvironment to elucidate the underlying mechanisms of immune evasion in cancers. Trogocytosis is a process where cells exchange membrane proteins, first noted in the 1970s, and it affects immune responses. Membrane proteins are molecules that help cells communicate and interact. Researchers emphasized its importance in how immune cells interact. This review discusses trogocytosis in the tumor microenvironment, influencing both immune and cancer cells. The study explains that trogocytosis allows cells to “nibble” on others, transferring membrane properties, which can change the function of immune cells like T cells and NK cells. Various methods were used to study these interactions, focusing on immune and cancer cells. Findings indicate that trogocytosis can either suppress or enhance immune responses, affecting cancer therapies such as CAR-T cells. Understanding trogocytosis could improve cancer treatments by adjusting immune responses, and future research might explore its mechanisms to boost immunotherapy. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"1-12"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01364-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing and spatial transcriptomics of esophageal squamous cell carcinoma with lymph node metastases","authors":"Wei Guo, Bolun Zhou, Lizhou Dou, Lei Guo, Yong Li, Jianjun Qin, Zhen Wang, Qilin Huai, Xuemin Xue, Yin Li, Jianming Ying, Qi Xue, Shugeng Gao, Jie He","doi":"10.1038/s12276-024-01369-x","DOIUrl":"10.1038/s12276-024-01369-x","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) patients often face a grim prognosis due to lymph node metastasis. However, a comprehensive understanding of the cellular and molecular characteristics of metastatic lymph nodes in ESCC remains elusive. In this study involving 12 metastatic ESCC patients, we employed single-cell sequencing, spatial transcriptomics (ST), and multiplex immunohistochemistry (mIHC) to explore the spatial and molecular attributes of primary tumor samples, adjacent tissues, metastatic and non-metastatic lymph nodes. The analysis of 161,333 cells revealed specific subclusters of epithelial cells that were significantly enriched in metastatic lymph nodes, suggesting pro-metastatic characteristics. Furthermore, stromal cells in the tumor microenvironment, including MMP3+IL24+ fibroblasts, APLN+ endothelial cells, and CXCL12+ pericytes, were implicated in ESCC metastasis through angiogenesis, collagen production, and inflammatory responses. Exhausted CD8+ T cells in a cycling status were notably prevalent in metastatic lymph nodes, indicating their potential role in facilitating metastasis. We identified distinct cell-cell communication networks and specific ligand-receptor pathways. Our findings were validated through a spatial transcriptome map and mIHC. This study enhances our comprehension of the cellular and molecular aspects of metastatic lymph nodes in ESCC patients, offering potential insights into novel therapeutic strategies for these individuals. Esophageal cancer is a severe disease with low survival rates, especially a type called esophageal squamous cell carcinoma. When cancer spreads to lymph nodes, it worsens the prognosis, indicating a need for better treatments. Wei Guo and colleagues studied immune cell interactions in ESCC to discover new therapies. They examined 12 ESCC patients using advanced techniques like single-cell RNA sequencing and spatial transcriptomics. These methods analyze individual cell types and their locations, helping to understand the tumor microenvironment, which is vital for cancer spread. The study identified that certain cells, such as epithelial cells and fibroblasts, play a role in metastasis. Targeting these cells might enhance treatment options. The findings emphasize that understanding TME interactions is crucial for developing new therapies, and future research could focus on these interactions to improve ESCC patient outcomes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"59-71"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01369-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of YTHDC1 m6A reading function promotes invasiveness in urothelial carcinoma of the bladder","authors":"Jinyun Xu, Jonas Koch, Claudia Schmidt, Malin Nientiedt, Manuel Neuberger, Philipp Erben, Maurice Stephan Michel, Manuel Rodríguez-Paredes, Frank Lyko","doi":"10.1038/s12276-024-01377-x","DOIUrl":"10.1038/s12276-024-01377-x","url":null,"abstract":"Bladder cancer poses significant clinical challenges due to its high metastatic potential and poor prognosis, especially when it progresses to muscle-invasive stages. Here, we show that the m6A reader YTHDC1 is downregulated in muscle-invasive bladder cancer and is negatively correlated with the expression of epithelial‒mesenchymal transition genes. The functional inhibition or depletion of YTHDC1 increased the migration and invasion of urothelial cells. Integrative analysis of multimodal sequencing datasets provided detailed insights into the molecular mechanisms mediating YTHDC1-dependent phenotypes and identified SMAD6 as a key transcript involved in the invasiveness of urothelial carcinoma of the bladder. Notably, SMAD6 mRNA colocalized less with YTHDC1 in tumoral tissues than in paratumoral tissues, indicating disrupted binding during cancer progression. Our findings establish YTHDC1-dependent m6A reading as a critical epitranscriptomic mechanism regulating bladder cancer invasiveness and provide a paradigm for the epitranscriptomic deregulation of cancer-associated networks. Bladder cancer is a common and potentially deadly disease affecting the urinary system. Researchers have identified a protein called YTHDC1, which reads specific RNA modifications (chemical changes to RNA that affect its function), as being less present in more aggressive cases of bladder cancer. This study investigates how YTHDC1 influences the invasiveness of cancer cells. The research involved analyzing bladder cancer samples and conducting experiments on cell models, using RNA sequencing (a method to study the sequence of RNA) and other techniques to understand YTHDC1’s role in cancer progression. Results indicated that lower levels of YTHDC1 are associated with increased cancer cell invasion and migration. The study concludes that YTHDC1 is crucial in preventing cancer spread by regulating specific genes. Future research could explore YTHDC1 as a potential target for bladder cancer treatment. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"118-130"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01377-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MT-100, a human Tie2-agonistic antibody, improves penile neurovasculature in diabetic mice via the novel target Srpx2","authors":"Fang-Yuan Liu, Young-Lai Cho, Fitri Rahma Fridayana, Lashkari Niloofar, Minh Nhat Vo, Yan Huang, Anita Limanjaya, Mi-Hye Kwon, Jiyeon Ock, Seon-Jin Lee, Guo Nan Yin, Nam-Kyung Lee, Ji-Kan Ryu","doi":"10.1038/s12276-024-01373-1","DOIUrl":"10.1038/s12276-024-01373-1","url":null,"abstract":"Diabetes is an incurable, chronic disease that can lead to many complications, including angiopathy, peripheral neuropathy, and erectile dysfunction (ED). The angiopoietin-Tie2 signaling pathway plays a critical role in blood vessel development, formation, remodeling, and peripheral nerve regeneration. Therefore, strategies for activating the Tie2 signaling pathway have been developed as potential therapies for neurovascular diseases. Here, we developed a human Tie2-agonistic antibody (MT-100) that not only resists Ang-2 antagonism and activates Tie2 signaling but also regulates a novel target, sushi repeat-containing protein X-linked 2 (Srpx2). This regulation led to the survival of vascular and neuronal cells, a reduction in the production of reactive oxygen species (ROS), activation of the PI3K/AKT/eNOS signaling pathway, increased expression of neurotrophic factors, and ultimately alleviation of ED in diabetic mice. Our findings not only provide conclusive evidence that MT-100 is a promising therapeutic strategy for the treatment of diabetic ED but also suggest it has substantial clinical applications for other complications associated with diabetes. Erectile dysfunction is a condition where men have difficulty maintaining an erection. It is common among men with diabetes, often due to severe damage to blood vessels. Researchers found a need for better therapies for diabetic ED. They created a new humanized antibody, MT-100, which targets the Tie2 receptor. The Tie2 receptor is important for keeping blood vessels stable and protecting nerves. In their study, they tested MT-100 on diabetic mice. After injecting MT-100, the mice showed better erectile function due to improved blood vessel and nerve growth. MT-100 also helped cells survive and reduced oxidative stress, which is damage caused by harmful molecules. The study suggests MT-100 could be a promising treatment for diabetic ED by supporting blood vessel and nerve health. Future studies might look at MT-100 for other blood vessel diseases. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"104-117"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01373-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of the β-catenin destruction complex via Ephexin1-Axin1 interaction promotes colorectal cancer proliferation","authors":"Jeeho Kim, Young Jin Jeon, In-Youb Chang, Jung-Hee Lee, Ho Jin You","doi":"10.1038/s12276-024-01381-1","DOIUrl":"10.1038/s12276-024-01381-1","url":null,"abstract":"Wnt signaling is essential for cell growth and tumor formation and is abnormally activated in colorectal cancer (CRC), contributing to tumor progression; however, the specific role and regulatory mechanisms involved in tumor development remain unclear. Here, we show that Ephexin1, a guanine nucleotide exchange factor, is significantly overexpressed in CRC and is correlated with increased Wnt/β-catenin pathway activity. Through comprehensive analysis, including RNA sequencing data from TCGA and functional assays, we observed that Ephexin1 promotes tumor proliferation and migration by activating the Wnt/β-catenin pathway. This effect was mediated by the interaction of Ephexin1 with Axin1, a critical component of the β-catenin destruction complex, which in turn enhanced the stability and activity of β-catenin in signaling pathways critical for tumor development. Importantly, our findings also suggest that targeting Ephexin1 may increase the efficacy of Wnt/β-catenin pathway inhibitors in CRC treatment. These findings highlight the potential of targeting Ephexin1 as a strategy for developing effective treatments for CRC, suggesting a novel and promising approach to therapy aimed at inhibiting cancer progression. Wnt signaling is crucial for cell growth and is often overactive in cancers like colorectal cancer (CRC). This study explores the role of a protein called Ephexin1 in CRC. Researchers found that Ephexin1 is overexpressed in CRC and promotes tumor growth by activating Wnt/β-catenin signaling. They used various cell lines and animal models to study this interaction. The study involved analyzing gene expression data from The Cancer Genome Atlas (TCGA) and conducting experiments to understand how Ephexin1 affects β-catenin stability, a key player in Wnt signaling. Results showed that reducing Ephexin1 levels made CRC cells more sensitive to Wnt inhibitors, suggesting that targeting Ephexin1 could enhance treatment efficacy. The researchers conclude that Ephexin1 is a potential therapeutic target for CRC, as it plays a significant role in Wnt signaling modulation. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"57 1","pages":"151-166"},"PeriodicalIF":9.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01381-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics","authors":"Kyungtaek Park, Ji-Hyang Lee, Eunsoon Shin, Hye Yoon Jang, Woo-Jung Song, Hyouk-Soo Kwon, Yoo Sook Cho, Jong Eun Lee, Ian Adcock, Kian Fan Chung, Jeong Seok Lee, Sungho Won, Tae-Bum Kim","doi":"10.1038/s12276-024-01368-y","DOIUrl":"10.1038/s12276-024-01368-y","url":null,"abstract":"Patients with severe eosinophilic asthma often require systemic medication, including corticosteroids and anti-type 2 (T2) cytokine biologics, to control the disease. While anti-IL5 and anti-IL4Rα antibodies suppress the effects of IL-4, IL-5 and IL-13, the molecular pathways modified by these biologics that are associated with clinical improvement remain unclear. Therefore, we aimed to describe the effects of T2-targeting biologics on the gene expression of blood immune cells. We conducted single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from eight patients with severe eosinophilic asthma treated with mepolizumab, reslizumab, or dupilumab. PBMCs were obtained before the initiation of biologics and at 1- and 6-month timepoints after the initiation of treatment to elucidate treatment-induced changes. During treatment, the proportions of T cells/natural killer (NK) cells, myeloid cells, and B cells did not change. However, the composition of classical monocytes (CMs) changed: IL1B+ CMs were reduced, and S100A+ CMs were increased. The subsets of T cells also changed, and significant downregulation of the NF-κB pathway was observed. The genes related to the NF-κB pathway were suppressed across T/NK, myeloid, and B cells. The transcriptional landscape did not significantly change after the first month of treatment, but marked changes occurred at six-month intervals. In conclusion, regardless of the type of biologics used, suppression of T2-mediated pathways ultimately reduces the expression of genes related to NF-κB signaling in circulating immune cells. Further studies are warranted to identify potential biomarkers related to treatment response and long-term outcomes. Clinical trial registration number: NCT05164939 Severe asthma is a chronic disease where the airways are inflamed, causing breathing issues even with high-dose inhaled corticosteroids. Current treatments, including biologics, help but don’t fully control the disease. Researchers studied how biologics affect immune cells in severe asthma patients. In this study, they analyzed blood samples from eight patients treated with biologics like mepolizumab, reslizumab, and dupilumab. They used single-cell RNA sequencingto examine changes in gene expression in immune cells over six months. The researchers found that biologics reduced inflammation by altering specific immune cell pathways. They observed a decrease in pro-inflammatory genes and an incrḍease in genes related to immune regulation. These changes suggest that biologics help control severe asthma by modifying immune cell behavior. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2755-2762"},"PeriodicalIF":9.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01368-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic reprogramming in mouse and human primordial germ cells","authors":"Sun-Min Lee, M. Azim Surani","doi":"10.1038/s12276-024-01359-z","DOIUrl":"10.1038/s12276-024-01359-z","url":null,"abstract":"Primordial germ cells (PGCs) are the precursors of sperm and eggs. They undergo genome-wide epigenetic reprogramming to erase epigenetic memory and reset the genomic potential for totipotency. Global DNA methylation erasure is a crucial part of epigenetic resetting when DNA methylation levels decrease across the genome to <5%. However, certain localized regions exhibit slower demethylation or resistance to reprogramming. Since DNA methylation plays a crucial role in transcriptional regulation, this depletion in PGCs requires mechanisms independent of DNA methylation to regulate transcriptional control during PGC reprogramming. Histone modifications are predicted to compensate for the loss of DNA methylation in gene regulation. Different histone modifications exhibit distinct patterns in PGCs undergoing epigenetic programming at the genomic level during PGC development in conjunction with changes in DNA methylation. Together, they contribute to PGC-specific genomic regulation. Recent findings related to these processes provide a comprehensive overview of germline epigenetic reprogramming and its importance in mouse and human PGC development. Additionally, we evaluated the extent to which in vitro culture techniques have replicated the development processes of human PGCs. Primordial germ cells (PGCs), which eventually become eggs or sperm, undergo unique and important changes early in their development that are crucial for forming a complete organism after fertilization. Recent studies have advanced our understanding of these changes. This review explains how certain processes, such as adding chemical markers to DNA (DNA methylation) and modifying proteins around DNA (histone modifications), control the development of PGCs in humans and mice. It also explores the replication of these processes in the lab using human stem cells. This review provides important insights into the impact of these changes on reproduction and offers potential new avenues for treating infertility. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2578-2587"},"PeriodicalIF":9.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01359-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Essential role of Card11 in airway hyperresponsiveness in high-fat diet-induced obese mice","authors":"Hyun-Seung Lee, Byung-Keun Kim, Suh-Young Lee, Hyuktae Kwon, Heung-Woo Park","doi":"10.1038/s12276-024-01367-z","DOIUrl":"10.1038/s12276-024-01367-z","url":null,"abstract":"A high-fat diet (HFD) can induce airway hyperresponsiveness (AHR) in obese mice, independent of allergic sensitization. This study aimed to identify the key molecules related to AHR in HFD-induced obese mice. In a cluster analysis of time series gene expression in the adipose and lung tissues of HFD-induced obese mice, we identified the Caspase Recruitment Domain Family Member 11 (Card11) gene as an essential molecule. We measured CARD11 expression in peripheral blood mononuclear cells (PBMCs) from obese individuals with asthma and performed Card11 signal inhibition in HFD-induced obese mice via Card11 siRNA. Card11 expression was significantly increased in M1 macrophages (IL-1β+CD11c+CD206- in CD11b+) in adipose tissue and in ILC3s (RORγt+ in IL7R+ of Lin-) in lung tissue from HFD-induced obese mice. In addition, CARD11+ populations among ILC3s and LPS-stimulated IL-1β+CD16+ monocytes from the PBMCs of obese individuals with asthma were significantly greater than those from obese controls or nonobese individuals with asthma. AHR in HFD-induced obese mice disappeared when we inhibited the Card11 signaling pathway by administering Card11 siRNA during the first or last seven weeks of the 13-week HFD feeding. Finally, we confirmed that Card11 siRNA decreased the number of M1 macrophages in adipose tissue and the number of ILC3s in lung tissue in vitro. Card11 significantly contributes to the development of AHR in HFD-induced obese mice by affecting immune cells in both adipose and lung tissues. The middle stage of HFD feeding seemed to be critical for these processes. Obesity is a metabolic disease and a major risk factor for several non-communicable diseases. The link between obesity and asthma is not fully understood. The study used a murine model to investigate how obesity affects asthma. Researchers fed mice a high-fat diet and analyzed gene expression in their adipose and lung tissues. They identified the Card11 gene as a key player in airway hyperresponsiveness in obese mice. This was an experimental study involving mice. Results showed that Card11 expression increased in immune cells from both adipose and lung tissues of obese mice. Inhibiting Card11 reduced AHR and inflammation. Researchers concluded that Card11 is crucial in obesity-related asthma. Future studies could explore Card11 as a therapeutic target for asthma in obese individuals. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2747-2754"},"PeriodicalIF":9.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01367-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GRIM-19-mediated induction of mitochondrial STAT3 alleviates systemic sclerosis by inhibiting fibrosis and Th2/Th17 cells","authors":"Ha Yeon Jeong, Jin-Sil Park, Jeong Won Choi, Kun Hee Lee, Seung Cheon Yang, Hye Yeon Kang, Sang Hee Cho, Seon-Yeong Lee, A Ram Lee, Youngjae Park, Sung-Hwan Park, Mi-La Cho","doi":"10.1038/s12276-024-01366-0","DOIUrl":"10.1038/s12276-024-01366-0","url":null,"abstract":"The gene associated with the retinoid–IFN-induced mortality-19 (GRIM-19) protein is a regulator of a cell death regulatory protein that inhibits STAT3, which is a critical transcription factor for interleukin (IL)-17-producing T (Th17) cells and a key integrator of extracellular matrix accumulation in systemic sclerosis (SSc). This protein is also a component of mitochondrial complex I, where it directly binds to STAT3 and recruits STAT3 to the mitochondria via the mitochondrial importer Tom20. In this study, the role of GRIM19 and its relationship with STAT3 in SSc development was investigated using a murine model of SSc. We observed a decrease in the level of GRIM-19 in the lesional skin of mice with bleomycin-induced SSc, which was negatively correlated with the level of STAT3. Overexpression of GRIM-19 reduced dermal thickness and fibrosis and the frequency of Th2 and Th17 cells in SSc mice. Mitophagic dysfunction promoted fibrosis in mice lacking PINK1, which is a mitophagy inducer. In an in vitro system, the overexpression of GRIM-19 increased the level of mitochondrial STAT3 (mitoSTAT3), induced mitophagy, and alleviated fibrosis progression. MitoSTAT3 overexpression hindered the development of bleomycin-induced SSc by reducing fibrosis. These results suggest that GRIM-19 is an effective therapeutic target for alleviating the development of SSc by increasing mitophagy. Systemic sclerosis is an autoimmune disease causing skin and organ fibrosis. The exact cause is unknown, but inflammation plays a key role. Researchers found a gap in understanding how the GRIM-19 protein affects SSc. Ha Yeon Jeong and colleagues conducted experiments on mice to explore this. The study involved injecting mice with a substance to induce SSc and then treating them with a GRIM-19 plasmid (a small DNA molecule). This experiment aimed to see if GRIM-19 could reduce fibrosis. The study type was an experiment involving 8-week-old male mice. Results showed that overexpression of GRIM-19 reduced skin thickness and inflammation in SSc mice. The researchers concluded that GRIM-19 helps control fibrosis by interacting with mitochondrial STAT3 (a protein involved in cell signaling). Future research could explore GRIM-19 as a potential treatment for SSc. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":"56 12","pages":"2739-2746"},"PeriodicalIF":9.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s12276-024-01366-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}