Disease Models & Mechanisms最新文献_第5页

A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation. 在头颈部癌症放疗后急性唾液腺损伤的小鼠模型中，单剂量放射与分次放射的效果相当。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-22 DOI: 10.1242/dmm.050733

Amanda L Johnson, Sonia S Elder, John G McKendrick, Lizi M Hegarty, Ella Mercer, Elaine Emmerson

{"title":"A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.","authors":"Amanda L Johnson, Sonia S Elder, John G McKendrick, Lizi M Hegarty, Ella Mercer, Elaine Emmerson","doi":"10.1242/dmm.050733","DOIUrl":"10.1242/dmm.050733","url":null,"abstract":"The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Muscle-specific lack of Gfpt1 triggers ER stress to alleviate misfolded protein accumulation. 基因敲入小鼠肌肉特异性缺乏 GFPT1 会引发 ER 应激，从而缓解折叠错误的蛋白质。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-07-25 DOI: 10.1242/dmm.050768

Ruchen Zhang, Paniz Farshadyeganeh, Bisei Ohkawara, Kazuki Nakajima, Jun-Ichi Takeda, Mikako Ito, Shaochuan Zhang, Yuki Miyasaka, Tamio Ohno, Madoka Mori-Yoshimura, Akio Masuda, Kinji Ohno

{"title":"Muscle-specific lack of Gfpt1 triggers ER stress to alleviate misfolded protein accumulation.","authors":"Ruchen Zhang, Paniz Farshadyeganeh, Bisei Ohkawara, Kazuki Nakajima, Jun-Ichi Takeda, Mikako Ito, Shaochuan Zhang, Yuki Miyasaka, Tamio Ohno, Madoka Mori-Yoshimura, Akio Masuda, Kinji Ohno","doi":"10.1242/dmm.050768","DOIUrl":"10.1242/dmm.050768","url":null,"abstract":"Pathogenic variants in GFPT1, encoding a key enzyme to synthesize UDP-N-acetylglucosamine (UDP-GlcNAc), cause congenital myasthenic syndrome (CMS). We made a knock-in (KI) mouse model carrying a frameshift variant in Gfpt1 exon 9, simulating that found in a patient with CMS. As Gfpt1 exon 9 is exclusively expressed in striated muscles, Gfpt1-KI mice were deficient for Gfpt1 only in skeletal muscles. In Gfpt1-KI mice, (1) UDP-HexNAc, CMP-NeuAc and protein O-GlcNAcylation were reduced in skeletal muscles; (2) aged Gfpt1-KI mice showed poor exercise performance and abnormal neuromuscular junction structures; and (3) markers of the unfolded protein response (UPR) were elevated in skeletal muscles. Denervation-mediated enhancement of endoplasmic reticulum (ER) stress in Gfpt1-KI mice facilitated protein folding, ubiquitin-proteasome degradation and apoptosis, whereas autophagy was not induced and protein aggregates were markedly increased. Lack of autophagy was accounted for by enhanced degradation of FoxO1 by increased Xbp1-s/u proteins. Similarly, in Gfpt1-silenced C2C12 myotubes, ER stress exacerbated protein aggregates and activated apoptosis, but autophagy was attenuated. In both skeletal muscles in Gfpt1-KI mice and Gfpt1-silenced C2C12 myotubes, maladaptive UPR failed to eliminate protein aggregates and provoked apoptosis.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A genetically small fetus impairs placental adaptations near term. 基因上的小胎儿会影响胎盘在临产前的适应能力。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-29 DOI: 10.1242/dmm.050719

Ionel Sandovici, Olatejumoye Knee, Jorge Lopez-Tello, Norman Shreeve, Abigail L Fowden, Amanda N Sferruzzi-Perri, Miguel Constância

{"title":"A genetically small fetus impairs placental adaptations near term.","authors":"Ionel Sandovici, Olatejumoye Knee, Jorge Lopez-Tello, Norman Shreeve, Abigail L Fowden, Amanda N Sferruzzi-Perri, Miguel Constância","doi":"10.1242/dmm.050719","DOIUrl":"10.1242/dmm.050719","url":null,"abstract":"The placenta is a gatekeeper between the mother and fetus, adapting its structure and functions to support optimal fetal growth. Studies exploring adaptations of placentae that support the development of genetically small fetuses are lacking. Here, using a mouse model of impaired fetal growth, achieved by deleting insulin-like growth factor 2 (Igf2) in the epiblast, we assessed placental nutrient transfer and umbilical artery (UA) blood flow during late gestation. At embryonic day (E) 15.5, we observed a decline in the trans-placental flux of glucose and system A amino acids (by using 3H-MeG and 14C-MeAIB), proportionate to the diminished fetal size, whereas UA blood flow was normal. However, at E18.5, the trans-placental flux of both tracers was disproportionately decreased and accompanied by blunted UA blood flow. Feto-placental growth and nutrient transfer were more impaired in female conceptuses. Thus, reducing the fetal genetic demand for growth impairs the adaptations in placental blood flow and nutrient transport that normally support the fast fetal growth during late gestation. These findings have important implications for our understanding of the pathophysiology of pregnancies afflicted by fetal growth restriction.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"17 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Fine-tuning AMPK in physiology and disease using point-mutant mouse models. 利用点突变小鼠模型微调 AMPK 在生理和疾病中的作用

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-13 DOI: 10.1242/dmm.050798

Naghmana Ashraf, Jeanine L Van Nostrand

{"title":"Fine-tuning AMPK in physiology and disease using point-mutant mouse models.","authors":"Naghmana Ashraf, Jeanine L Van Nostrand","doi":"10.1242/dmm.050798","DOIUrl":"10.1242/dmm.050798","url":null,"abstract":"AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that monitors the cellular energy status to adapt it to the fluctuating nutritional and environmental conditions in an organism. AMPK plays an integral part in a wide array of physiological processes, such as cell growth, autophagy and mitochondrial function, and is implicated in diverse diseases, including cancer, metabolic disorders, cardiovascular diseases and neurodegenerative diseases. AMPK orchestrates many different physiological outcomes by phosphorylating a broad range of downstream substrates. However, the importance of AMPK-mediated regulation of these substrates in vivo remains an ongoing area of investigation to better understand its precise role in cellular and metabolic homeostasis. Here, we provide a comprehensive overview of our understanding of the kinase function of AMPK in vivo, as uncovered from mouse models that harbor phosphorylation mutations in AMPK substrates. We discuss some of the inherent limitations of these mouse models, highlight the broader implications of these studies for understanding human health and disease, and explore the valuable insights gained that could inform future therapeutic strategies for the treatment of metabolic and non-metabolic disorders.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"17 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Functional distinction in oncogenic Ras variant activity in Caenorhabditis elegans. 草履虫致癌 Ras 变异活动的功能性区别

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-14 DOI: 10.1242/dmm.050577

Haimeng Lyu, Helen M Chamberlin

{"title":"Functional distinction in oncogenic Ras variant activity in Caenorhabditis elegans.","authors":"Haimeng Lyu, Helen M Chamberlin","doi":"10.1242/dmm.050577","DOIUrl":"10.1242/dmm.050577","url":null,"abstract":"Ras genes are important oncogenes that are frequently mutated in cancer. Human oncogenic variants exhibit functional distinctions in terms of their representation in different cancer types, impact on cellular targets and sensitivity to pharmacological treatments. However, how these distinct variants influence and respond to the cellular networks in which they are embedded is poorly understood. To identify novel participants in the complex interplay between Ras genotype and cell interaction networks in vivo, we have developed and tested an experimental framework using a simple vulva-development assay in the nematode C. elegans. Using this system, we evaluated a set of Ras oncogenic substitution changes at G12, G13 and Q61. We found that these variants fall into distinct groups based on phenotypic differences, sensitivity to gene dosage and inhibition of the downstream kinase MEK and their response to genetic modulators that influence Ras activity in a non-autonomous manner. Together, our results demonstrated that oncogenic C. elegans Ras variants exhibit clear distinctions in how they interface with the vulva-development network and showed that extracellular modulators yield variant-restricted effects in vivo.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A deleterious variant of INTS1 leads to disrupted sleep-wake cycles. INTS1的有害变体会导致睡眠-觉醒周期紊乱。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-27 DOI: 10.1242/dmm.050746

Shir Confino, Yair Wexler, Adar Medvetzky, Yotam Elazary, Zohar Ben-Moshe, Joel Reiter, Talya Dor, Simon Edvardson, Gali Prag, Tamar Harel, Yoav Gothilf

{"title":"A deleterious variant of INTS1 leads to disrupted sleep-wake cycles.","authors":"Shir Confino, Yair Wexler, Adar Medvetzky, Yotam Elazary, Zohar Ben-Moshe, Joel Reiter, Talya Dor, Simon Edvardson, Gali Prag, Tamar Harel, Yoav Gothilf","doi":"10.1242/dmm.050746","DOIUrl":"10.1242/dmm.050746","url":null,"abstract":"Sleep disturbances are common among children with neurodevelopmental disorders. Here, we report a syndrome characterized by prenatal microcephaly, intellectual disability and severe disruption of sleep-wake cycles in a consanguineous family. Exome sequencing revealed homozygous variants (c.5224G>A and c.6506G>T) leading to the missense mutations E1742K and G2169V in integrator complex subunit 1 (INTS1), the core subunit of the Integrator complex. Conservation and structural analyses suggest that G2169V has a minor impact on the structure and function of the complex, while E1742K significantly alters a negatively charged conserved patch on the surface of the protein. The severe sleep-wake cycles disruption in human carriers highlights a new aspect of Integrator complex impairment. To further study INTS1 pathogenicity, we generated Ints1-deficient zebrafish lines. Mutant zebrafish larvae displayed abnormal circadian rhythms of locomotor activity and sleep, as is the case with the affected humans. Furthermore, Ints1-deficent larvae exhibited elevated levels of dopamine β-hydroxylase (dbh) mRNA in the locus coeruleus, a wakefulness-inducing brainstem center. Altogether, these findings suggest a significant, likely indirect, effect of INTS1 and the Integrator complex on maintaining circadian rhythms of locomotor activity and sleep homeostasis across vertebrates.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"17 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11381918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Macrophages directly kill bladder cancer cells through TNF signaling as an early response to BCG therapy. 巨噬细胞通过 TNF 信号直接杀死膀胱癌细胞，这是卡介苗疗法的早期反应。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-08-08 DOI: 10.1242/dmm.050693

Mayra Fernanda Martínez-López, Cátia Rebelo de Almeida, Márcia Fontes, Raquel Valente Mendes, Stefan H E Kaufmann, Rita Fior

{"title":"Macrophages directly kill bladder cancer cells through TNF signaling as an early response to BCG therapy.","authors":"Mayra Fernanda Martínez-López, Cátia Rebelo de Almeida, Márcia Fontes, Raquel Valente Mendes, Stefan H E Kaufmann, Rita Fior","doi":"10.1242/dmm.050693","DOIUrl":"10.1242/dmm.050693","url":null,"abstract":"The Bacillus Calmette-Guérin (BCG) vaccine is the oldest cancer immunotherapeutic agent in use. Despite its effectiveness, its initial mechanisms of action remain largely unknown. Here, we elucidate the earliest cellular mechanisms involved in BCG-induced tumor clearance. We developed a fast preclinical in vivo assay to visualize in real time and at single-cell resolution the initial interactions among bladder cancer cells, BCG and innate immunity using the zebrafish xenograft model. We show that BCG induced the recruitment and polarization of macrophages towards a pro-inflammatory phenotype, accompanied by induction of the inflammatory cytokines tnfa, il1b and il6 in the tumor microenvironment. Macrophages directly induced apoptosis of human cancer cells through zebrafish TNF signaling. Macrophages were crucial for this response as their depletion completely abrogated the BCG-induced phenotype. Contrary to the general concept that macrophage anti-tumoral activities mostly rely on stimulating an effective adaptive response, we demonstrate that macrophages alone can induce tumor apoptosis and clearance. Thus, our results revealed an additional step to the BCG-induced tumor immunity model, while providing proof-of-concept experiments demonstrating the potential of this unique model to test innate immunomodulators.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"17 8","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

HBS1L deficiency causes retinal dystrophy in a child and in a mouse model associated with defective development of photoreceptor cells. HBS1L 缺乏症会导致儿童视网膜营养不良，小鼠模型与感光细胞发育缺陷有关。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-08-01 Epub Date: 2024-07-30 DOI: 10.1242/dmm.050557

Shiyu Luo, Bilal Alwattar, Qifei Li, Kiran Bora, Alexandra K Blomfield, Jasmine Lin, Anne Fulton, Jing Chen, Pankaj B Agrawal

{"title":"HBS1L deficiency causes retinal dystrophy in a child and in a mouse model associated with defective development of photoreceptor cells.","authors":"Shiyu Luo, Bilal Alwattar, Qifei Li, Kiran Bora, Alexandra K Blomfield, Jasmine Lin, Anne Fulton, Jing Chen, Pankaj B Agrawal","doi":"10.1242/dmm.050557","DOIUrl":"10.1242/dmm.050557","url":null,"abstract":"Inherited retinal diseases encompass a genetically diverse group of conditions caused by variants in genes critical to retinal function, including handful of ribosome-associated genes. This study focuses on the HBS1L gene, which encodes for the HBS1-like translational GTPase that is crucial for ribosomal rescue. We have reported a female child carrying biallelic HBS1L variants, manifesting with poor growth and neurodevelopmental delay. Here, we describe the ophthalmologic findings in the patient and in Hbs1ltm1a/tm1a hypomorph mice and describe the associated microscopic and molecular perturbations. The patient has impaired visual function, showing dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound thinning of the entire retina, specifically of the outer photoreceptor layer, due to extensive photoreceptor cell apoptosis. Loss of Hbs1l resulted in comprehensive proteomic alterations by mass spectrometry analysis, with an increase in the levels of 169 proteins and a decrease in the levels of 480 proteins, including rhodopsin (Rho) and peripherin 2 (Prph2). Gene Ontology biological process and gene set enrichment analyses reveal that the downregulated proteins are primarily involved in phototransduction, cilium assembly and photoreceptor cell development. These findings underscore the importance of ribosomal rescue proteins in maintaining retinal health, particularly in photoreceptor cells.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Male germ cell-associated kinase is required for axoneme formation during ciliogenesis in zebrafish photoreceptors. 雄性生殖细胞相关激酶（MAK）是斑马鱼光感受器纤毛形成过程中轴丝形成所必需的。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-07-01 Epub Date: 2024-07-16 DOI: 10.1242/dmm.050618

Hung-Ju Chiang, Yuko Nishiwaki, Wei-Chieh Chiang, Ichiro Masai

{"title":"Male germ cell-associated kinase is required for axoneme formation during ciliogenesis in zebrafish photoreceptors.","authors":"Hung-Ju Chiang, Yuko Nishiwaki, Wei-Chieh Chiang, Ichiro Masai","doi":"10.1242/dmm.050618","DOIUrl":"10.1242/dmm.050618","url":null,"abstract":"Vertebrate photoreceptors are highly specialized retinal neurons that have cilium-derived membrane organelles called outer segments, which function as platforms for phototransduction. Male germ cell-associated kinase (MAK) is a cilium-associated serine/threonine kinase, and its genetic mutation causes photoreceptor degeneration in mice and retinitis pigmentosa in humans. However, the role of MAK in photoreceptors is not fully understood. Here, we report that zebrafish mak mutants show rapid photoreceptor degeneration during embryonic development. In mak mutants, both cone and rod photoreceptors completely lacked outer segments and underwent apoptosis. Interestingly, zebrafish mak mutants failed to generate axonemes during photoreceptor ciliogenesis, whereas basal bodies were specified. These data suggest that Mak contributes to axoneme development in zebrafish, in contrast to mouse Mak mutants, which have elongated photoreceptor axonemes. Furthermore, the kinase activity of Mak was found to be critical in ciliary axoneme development and photoreceptor survival. Thus, Mak is required for ciliogenesis and outer segment formation in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Contribution of Streptococcus pseudopneumoniae and Streptococcus salivarius to vocal fold mucosal integrity and function. 假肺炎链球菌和唾液球菌对声带粘膜完整性和功能的影响

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2024-07-01 Epub Date: 2024-07-16 DOI: 10.1242/dmm.050670

Vlasta Lungova, Madhu Gowda, Jessica M Fernandez, Stephanie Bartley, Anumitha Venkatraman, Federico E Rey, Susan L Thibeault

{"title":"Contribution of Streptococcus pseudopneumoniae and Streptococcus salivarius to vocal fold mucosal integrity and function.","authors":"Vlasta Lungova, Madhu Gowda, Jessica M Fernandez, Stephanie Bartley, Anumitha Venkatraman, Federico E Rey, Susan L Thibeault","doi":"10.1242/dmm.050670","DOIUrl":"10.1242/dmm.050670","url":null,"abstract":"Structural changes to the vocal fold (VF) epithelium, namely, loosened intercellular junctions, have been reported in VF benign lesions. The potential mechanisms responsible for the disruption of cell junctions do not address the contribution of resident microbial communities to this pathological phenomenon. In this study, we focused on determining the relationship between Streptococcus pseudopneumoniae (SP), a dominant bacterial species associated with benign lesions, and Streptococcus salivarius (SS), a commensal bacterium, with human VF epithelial cells in our three-dimensional model of the human VF mucosa. This experimental system enabled direct deposition of bacteria onto constructs at the air/liquid interface, allowing for the assessment of bacterium-host interactions at the cellular, molecular and ultrastructural levels. Our findings demonstrate that SP disrupts VF epithelial integrity and initiates inflammation via the exported products HtrA1 and pneumolysin. In contrast, SS attaches to the VF epithelium, reduces inflammation and induces Mmp2-mediated apical desquamation of infected cells to mitigate the impact of pathogens. In conclusion, this study highlights the complexity of microbial involvement in VF pathology and potential VF mucosal restoration in the presence of laryngeal commensals.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11273296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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