Journal of Cellular and Molecular Medicine最新文献_第10页

Ion channels and transporters regulate nutrient absorption in health and disease 离子通道和转运体调节健康和疾病中的营养吸收

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-28 DOI: 10.1111/jcmm.17853

Xianmin Lu, Chen Luo, Jiangbo Wu, Ya Deng, Xingyi Mu, Ting Zhang, Xiaoxu Yang, Qi Liu, Zhuo Li, Siqi Tang, Yanxia Hu, Qian Du, Jingyu Xu, Rui Xie

{"title":"Ion channels and transporters regulate nutrient absorption in health and disease","authors":"Xianmin Lu, Chen Luo, Jiangbo Wu, Ya Deng, Xingyi Mu, Ting Zhang, Xiaoxu Yang, Qi Liu, Zhuo Li, Siqi Tang, Yanxia Hu, Qian Du, Jingyu Xu, Rui Xie","doi":"10.1111/jcmm.17853","DOIUrl":"10.1111/jcmm.17853","url":null,"abstract":"Ion channels and transporters are ubiquitously expressed on cell membrane, which involve in a plethora of physiological process such as contraction, neurotransmission, secretion and so on. Ion channels and transporters is of great importance to maintaining membrane potential homeostasis, which is essential to absorption of nutrients in gastrointestinal tract. Most of nutrients are electrogenic and require ion channels and transporters to absorb. This review summarizes the latest research on the role of ion channels and transporters in regulating nutrient uptake such as K+ channels, Ca2+ channels and ion exchangers. Revealing the mechanism of ion channels and transporters associated with nutrient uptake will be helpful to provide new methods to diagnosis and find potential targets for diseases like diabetes, inflammatory bowel diseases, etc. Even though some of study still remain ambiguous and in early stage, we believe that ion channels and transporters will be novel therapeutic targets in the future.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2631-2642"},"PeriodicalIF":5.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17853","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226736","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}

引用次数: 1

Androgen receptor agonist and antagonist reduce response of cytokine-induced killer cells on prostate cancer cells 雄激素受体激动剂和拮抗剂降低细胞因子诱导的杀伤细胞对前列腺癌症细胞的反应。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-28 DOI: 10.1111/jcmm.17923

Thanakorn Pungsrinont, Margret Ann Schneider, Aria Baniahmad

{"title":"Androgen receptor agonist and antagonist reduce response of cytokine-induced killer cells on prostate cancer cells","authors":"Thanakorn Pungsrinont, Margret Ann Schneider, Aria Baniahmad","doi":"10.1111/jcmm.17923","DOIUrl":"10.1111/jcmm.17923","url":null,"abstract":"Despite many advances, prostate cancer (PCa) is still the second most frequently diagnosed cancer and fifth leading cause of cancer death in men worldwide. So far, the promising field of onco-immunology has not yet provided a satisfactory treatment option for PCa. Here we show that the ex vivo expansion and activation of cytokine-induced killer (CIK) cells isolated from primary peripheral blood mononuclear cells induce immune-mediated apoptosis in both human PCa LNCaP and C4-2 cells. Interestingly, pretreating LNCaP and C4-2 cells with either androgen or the androgen receptor (AR) antagonist enzalutamide mediates resistance to this immunogenic attack. This is associated with a reduction of both total cell loss and apoptosis levels suggesting one possible mechanism blunting onco-immunological activity. The data also suggest that secreted factors from AR ligand-treated PCa cell suppress lymphocyte proliferation. Further, we analysed immune-mediated killing activity using conditioned media from LNCaP and C4-2 treated cells. The obtained data suggest that the conditioned media from PCa treated cells does not influence a measurable lymphocyte-mediated apoptosis. However, analysing clonal expansion of activated lymphocytes, the androgen-derived conditioned media suppresses lymphocyte proliferation/expansion suggesting inhibition of onco-immunological activity by pretreatment of PCa cells with AR ligands.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2970-2982"},"PeriodicalIF":5.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17923","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111181","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}

引用次数: 0

Environmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis 环境相关双酚A暴露通过调节microRNA生物发生促进卵巢癌的发生

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-23 DOI: 10.1111/jcmm.17920

Sophia S. N. Lam, Zeyu Shi, Carman K. M. Ip, Chris K. C. Wong, Alice S. T. Wong

{"title":"Environmental-relevant bisphenol A exposure promotes ovarian cancer stemness by regulating microRNA biogenesis","authors":"Sophia S. N. Lam, Zeyu Shi, Carman K. M. Ip, Chris K. C. Wong, Alice S. T. Wong","doi":"10.1111/jcmm.17920","DOIUrl":"10.1111/jcmm.17920","url":null,"abstract":"Bisphenol A (BPA) is a ubiquitous environmental xenobiotic impacting millions of people worldwide. BPA has long been proposed to promote ovarian carcinogenesis, but the detrimental mechanistic target remains unclear. Cancer stem cells (CSCs) are considered as the trigger of tumour initiation and progression. Here, we show for the first time that nanomolar (environmentally relevant) concentration of BPA can markedly increase the formation and expansion of ovarian CSCs concomitant. This effect is observed in both oestrogen receptor (ER)-positive and ER-defective ovarian cancer cells, suggesting that is independent of the classical ERs. Rather, the signal is mediated through alternative ER G-protein-coupled receptor 30 (GPR30), but not oestrogen-related receptor α and γ. Moreover, we report a novel role of BPA in the regulation of Exportin-5 that led to dysregulation of microRNA biogenesis through miR-21. The use of GPR30 siRNA or antagonist to inhibit GPR30 expression or activity, respectively, resulted in significant inhibition of ovarian CSCs. Similarly, the CSCs phenotype can be reversed by expression of Exportin-5 siRNA. These results identify for the first time non-classical ER and microRNA dysregulation as novel mediators of low, physiological levels of BPA function in CSCs that may underlie its significant tumour-promoting properties in ovarian cancer.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2792-2803"},"PeriodicalIF":5.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17920","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10577160","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}

引用次数: 0

27-Hydroxycholesterol represses G9a expression via oestrogen receptor alpha in breast cancer 羟基胆固醇通过雌激素受体α抑制乳腺癌中G9a的表达

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-23 DOI: 10.1111/jcmm.17882

Ravindran Vini, Asha Lekshmi, Swathy Ravindran, Jissa Vinoda Thulaseedharan, Kunjuraman Sujathan, Arumugam Rajavelu, Sreeharshan Sreeja

{"title":"27-Hydroxycholesterol represses G9a expression via oestrogen receptor alpha in breast cancer","authors":"Ravindran Vini, Asha Lekshmi, Swathy Ravindran, Jissa Vinoda Thulaseedharan, Kunjuraman Sujathan, Arumugam Rajavelu, Sreeharshan Sreeja","doi":"10.1111/jcmm.17882","DOIUrl":"10.1111/jcmm.17882","url":null,"abstract":"27-hydroxycholesterol (27-HC) is a cholesterol metabolite and the first discovered endogenous selective estrogen receptor modulator (SERM) that has been shown to have proliferative and metastatic activity in breast cancer. However, whether 27-HC metabolite modulates the epigenetic signatures in breast cancer and its progression remains unclear. The current study, reports that 27-HC represses the expression of euchromatic histone lysine methyltransferase G9a, further reducing di-methylation at H3K9 in a subset of genes. We also observed reduced occupancy of ERα at the G9a promoter, indicating that 27-HC negatively regulates the ERα occupancy on the G9a promoter and functions as a transcriptional repressor. Further, ChIP-sequencing for the H3K9me2 mark has demonstrated that 27-HC treatment reduces the H3K9me2 mark on subset of genes linked to cancer progression, proliferation, and metastasis. We observed upregulation of these genes following 27-HC treatment which further confirms the loss of methylation at these genes. Immunohistochemical analysis with breast cancer patient tissues indicated a positive correlation between G9a expression and CYP7B1, a key enzyme of 27-HC catabolism. Overall, this study reports that 27-HC represses G9a expression via ERα and reduces the levels of H3K9me2 on a subset of genes, including the genes that aid in breast tumorigenesis and invasion further, increasing its expression in the breast cancer cells.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2744-2755"},"PeriodicalIF":5.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232251","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}

引用次数: 0

Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice 八子补肾通过调节SAMP6小鼠的皮肤稳态来缓解皮肤衰老

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-23 DOI: 10.1111/jcmm.17833

Zhe Xu, Boyang Gong, Zhaodong Li, Ying Wang, Zeyu Zhao, Lulu Xie, Yanfei Peng, Shuwu Zhao, Huifang Zhou, Yuhong Bian

{"title":"Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice","authors":"Zhe Xu, Boyang Gong, Zhaodong Li, Ying Wang, Zeyu Zhao, Lulu Xie, Yanfei Peng, Shuwu Zhao, Huifang Zhou, Yuhong Bian","doi":"10.1111/jcmm.17833","DOIUrl":"10.1111/jcmm.17833","url":null,"abstract":"Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-β-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1β, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2651-2660"},"PeriodicalIF":5.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226719","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}

引用次数: 0

The rejuvenating influence of young plasma on aged intestine 青年血浆对衰老肠道的恢复作用

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-23 DOI: 10.1111/jcmm.17926

Taha Ceylani, Hikmet Taner Teker, Seda Keskin, Gizem Samgane, Eda Acikgoz, Rafig Gurbanov

{"title":"The rejuvenating influence of young plasma on aged intestine","authors":"Taha Ceylani, Hikmet Taner Teker, Seda Keskin, Gizem Samgane, Eda Acikgoz, Rafig Gurbanov","doi":"10.1111/jcmm.17926","DOIUrl":"10.1111/jcmm.17926","url":null,"abstract":"This study aims to investigate the effects of plasma exchange on the biomolecular profiles and histology of ileum and colon tissues in young and aged Sprague–Dawley male rats. Fourier transform infrared (FTIR) spectroscopy, linear discriminant analysis and support vector machine (SVM) techniques were employed to analyse the lipid, protein, and nucleic acid indices in young and aged rats. Following the application of young plasma, aged rats demonstrated biomolecular profiles similar to those of their younger counterparts. Histopathological and immunohistochemical assessments showed that young plasma had a protective effect on the intestinal tissues of aged rats, increasing cell density and reducing inflammation. Additionally, the expression levels of key inflammatory mediators tumour necrosis factor-alpha and cyclooxygenase-2 significantly decreased after young plasma administration. These findings underscore the therapeutic potential of young plasma for mitigating age-related changes and inflammation in the intestinal tract. They highlight the critical role of plasma composition in the ageing process and suggest the need for further research to explore how different regions of the intestines respond to plasma exchange. Such understanding could facilitate the development of innovative therapies targeting the gastrointestinal system, enhancing overall health during ageing.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2804-2816"},"PeriodicalIF":5.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17926","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10283165","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}

引用次数: 2

Challenges in anti-aging medicine–trends in biomarker discovery and therapeutic interventions for a healthy lifespan 抗衰老医学的挑战——生物标志物发现的趋势和健康寿命的治疗干预

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-23 DOI: 10.1111/jcmm.17912

Iuliana Popescu, Joris Deelen, Maddalena Illario, Jan Adams

{"title":"Challenges in anti-aging medicine–trends in biomarker discovery and therapeutic interventions for a healthy lifespan","authors":"Iuliana Popescu, Joris Deelen, Maddalena Illario, Jan Adams","doi":"10.1111/jcmm.17912","DOIUrl":"10.1111/jcmm.17912","url":null,"abstract":"We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle-independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno-antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 18","pages":"2643-2650"},"PeriodicalIF":5.3,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10595298","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}

引用次数: 0

Programmed cell death pathways as targets for developing antifilarial drugs: Lessons from the recent findings 程序化细胞死亡途径作为开发抗丝虫药物的靶点：从最近的发现中吸取的教训。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-22 DOI: 10.1111/jcmm.17913

Nabarun Chandra Das, Pritha Chakraborty, Samapika Nandy, Abhijit Dey, Tabarak Malik, Suprabhat Mukherjee

{"title":"Programmed cell death pathways as targets for developing antifilarial drugs: Lessons from the recent findings","authors":"Nabarun Chandra Das, Pritha Chakraborty, Samapika Nandy, Abhijit Dey, Tabarak Malik, Suprabhat Mukherjee","doi":"10.1111/jcmm.17913","DOIUrl":"10.1111/jcmm.17913","url":null,"abstract":"More than half a century has passed since the introduction of the National Filariasis Control Program; however, as of 2023, lymphatic filariasis (LF) still prevails globally, particularly in the tropical and subtropical regions, posing a substantial challenge to the objective of worldwide elimination. LF is affecting human beings and its economically important livestock leading to a crucial contributor to morbidities and disabilities. The current scenario has been blowing up alarms of attention to develop potent therapeutics and strategies having efficiency against the adult stage of filarial nematodes. In this context, the exploration of a suitable drug target that ensures lethality to macro and microfilariae is now our first goal to achieve. Apoptosis has been the potential target across all three stages of filarial nematodes viz. oocytes, microfilariae (mf) and adults resulting in filarial death after receiving the signal from the reactive oxygen species (ROS) and executed through intrinsic and extrinsic pathways. Hence, it is considered a leading target for developing antifilarial drugs. Herein, we have shown the efficacy of several natural and synthetic compounds/nanoformulations in triggering the apoptotic death of filarial parasites with little or no toxicity to the host body system.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2819-2840"},"PeriodicalIF":5.3,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396086","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}

引用次数: 1

OPA1, a molecular regulator of dilated cardiomyopathy OPA1，扩张型心肌病的分子调节因子。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-21 DOI: 10.1111/jcmm.17918

Jiaqi Chen, Jianan Shao, Yaoyao Wang, Kangxiang Wu, Mingyuan Huang

{"title":"OPA1, a molecular regulator of dilated cardiomyopathy","authors":"Jiaqi Chen, Jianan Shao, Yaoyao Wang, Kangxiang Wu, Mingyuan Huang","doi":"10.1111/jcmm.17918","DOIUrl":"10.1111/jcmm.17918","url":null,"abstract":"Dilated cardiomyopathy (DCM) is a disease with no specific treatment, poor prognosis and high mortality. During DCM development, there is apoptosis, mitochondrial dynamics imbalance and changes in cristae structure. Optic atrophy 1 (OPA1) appears at high frequency in these three aspects. DCM LMNA (LaminA/C) gene mutation can activate TP53, and the study of P53 shows that P53 affects OPA1 through Bak/Bax and OMA1 (a metalloprotease). OPA1 can be considered the missing link between DCMp53 and DCM apoptosis, mitochondrial dynamics imbalance and changes in cristae structure. OPA1 regulates apoptosis by regulating the release of cytochrome c from the mitochondrial matrix through CJs (crisp linkages, located in the inner mitochondrial membrane) and unbalances mitochondrial fusion and fission by affecting mitochondrial inner membrane (IM) fusion. OPA1 is also associated with the formation and maintenance of mitochondrial cristae. OPA1 is not the root cause of DCM, but it is an essential mediator in P53 mediating the occurrence and development of DCM, so OPA1 also becomes a molecular regulator of DCM. This review discusses the implication of OPA1 for DCM from three aspects: apoptosis, mitochondrial dynamics and ridge structure.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 20","pages":"3017-3025"},"PeriodicalIF":5.3,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17918","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10035101","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}

引用次数: 1

Epigenetic histone modification by butyrate downregulates KIT and attenuates mast cell function 丁酸修饰表观遗传组蛋白下调KIT并减弱肥大细胞功能。

IF 5.3 2区医学

Journal of Cellular and Molecular Medicine Pub Date : 2023-08-21 DOI: 10.1111/jcmm.17924

Ravindra Gudneppanavar, Emma Elizabeth Sabu Kattuman, Lakshminarayan Reddy Teegala, Erik Southard, Ramakumar Tummala, Bina Joe, Charles K. Thodeti, Sailaja Paruchuri

{"title":"Epigenetic histone modification by butyrate downregulates KIT and attenuates mast cell function","authors":"Ravindra Gudneppanavar, Emma Elizabeth Sabu Kattuman, Lakshminarayan Reddy Teegala, Erik Southard, Ramakumar Tummala, Bina Joe, Charles K. Thodeti, Sailaja Paruchuri","doi":"10.1111/jcmm.17924","DOIUrl":"10.1111/jcmm.17924","url":null,"abstract":"Short-chain fatty acid butyrate is produced from the bacterial fermentation of indigestible fiber in the intestinal lumen, and it has been shown to attenuate lung inflammation in murine asthma models. Mast cells (MCs) are initiators of inflammatory response to allergens, and they play an important role in asthma. MC survival and proliferation is regulated by its growth factor stem cell factor (SCF), which acts through the receptor, KIT. It has previously been shown that butyrate attenuates the activation of MCs by allergen stimulation. However, how butyrate mechanistically influences SCF signalling to impact MC function remains unknown. Here, we report that butyrate treatment triggered the modification of MC histones via butyrylation and acetylation, and inhibition of histone deacetylase (HDAC) activity. Further, butyrate treatment caused downregulation of SCF receptor KIT and associated phosphorylation, leading to significant attenuation of SCF-mediated MC proliferation, and pro-inflammatory cytokine secretion. Mechanistically, butyrate inhibited MC function by suppressing KIT and downstream p38 and Erk phosphorylation, and it mediated these effects via modification of histones, acting as an HDAC inhibitor and not via its traditional GPR41 (FFAR3) or GPR43 (FFAR2) butyrate receptors. In agreement, the pharmacological inhibition of Class I HDAC (HDAC1/3) mirrored butyrate's effects, suggesting that butyrate impacts MC function by HDAC1/3 inhibition. Taken together, butyrate epigenetically modifies histones and downregulates the SCF/KIT/p38/Erk signalling axis, leading to the attenuation of MC function, validating its ability to suppress MC-mediated inflammation. Therefore, butyrate supplementations could offer a potential treatment strategy for allergy and asthma via epigenetic alterations in MCs.","PeriodicalId":15215,"journal":{"name":"Journal of Cellular and Molecular Medicine","volume":"27 19","pages":"2983-2994"},"PeriodicalIF":5.3,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.17924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096355","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}

引用次数: 0