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Amy and Friends: improving the lives of individuals affected by DNA repair disorders 艾米和朋友们：改善受DNA修复障碍影响的个体的生活。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-05 DOI: 10.1002/1873-3468.70049
Jayne Hughes, Donata Orioli, Lavinia Arseni
{"title":"Amy and Friends: improving the lives of individuals affected by DNA repair disorders","authors":"Jayne Hughes,&nbsp;Donata Orioli,&nbsp;Lavinia Arseni","doi":"10.1002/1873-3468.70049","DOIUrl":"10.1002/1873-3468.70049","url":null,"abstract":"<p>DNA repair disorders are rare genetic conditions characterized by defects in the mechanisms responsible for repairing damaged DNA. DNA damage occurs frequently due to environmental factors, and in healthy cells, repair systems fix this damage to maintain genomic integrity. In individuals with DNA repair disorders, these mechanisms are impaired, leading to accumulated damage, cellular dysfunction, premature aging, and cell death. Symptoms vary depending on the specific repair pathway defect, with examples including Cockayne syndrome (CS), trichothiodystrophy (TTD), and xeroderma pigmentosum. <i>Amy and Friends</i> was founded by Jayne Hughes in the UK in 2007 to support children/young adults and families suffering from CS, TTD, and linked DNA repair disorders. In this second of a new series on patient advocacy, <i>FEBS Letters</i> interviews Founder and CEO Jayne Hughes and molecular geneticist and specialist team member Prof. Donata Orioli on the aims, achievements, and activities of <i>Amy and Friends</i>.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 10","pages":"1339-1345"},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protonophore activity of short-chain fatty acids induces their intracellular accumulation and acidification. 短链脂肪酸的质子团活性诱导其在细胞内积累和酸化。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-05 DOI: 10.1002/1873-3468.70064
Muwei Jiang, Frans Bianchi, Geert van den Bogaart
{"title":"Protonophore activity of short-chain fatty acids induces their intracellular accumulation and acidification.","authors":"Muwei Jiang, Frans Bianchi, Geert van den Bogaart","doi":"10.1002/1873-3468.70064","DOIUrl":"https://doi.org/10.1002/1873-3468.70064","url":null,"abstract":"<p><p>Short-chain fatty acids (SCFAs), produced by dietary fiber fermentation in the colon, play essential roles in cellular metabolism, with butyrate notably modulating immune responses and epigenetic regulation. Their production contributes to an acidic colonic environment where protonated SCFAs permeate membranes, leading to intracellular acidification and SCFA accumulation. Using our method to measure intracellular pH, we investigated how extracellular pH influences butyrate-induced acidification and immunomodulatory effects in human macrophages. Our data show that butyrate accumulates and acidifies cells at acidic extracellular pH due to the permeability of its protonated form. While inflammatory cytokine production was mildly influenced by extracellular pH, butyrate-induced histone acetylation exhibited a pH dependence, underscoring the importance of considering extracellular pH when assessing the SCFA's functions.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spot-14 and its paralog Spot-14R regulate expression of metabolic and thermogenic pathway genes in murine brown and beige adipocytes Spot-14及其类似物Spot-14R调节小鼠棕色和米色脂肪细胞的代谢和产热途径基因的表达。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-02 DOI: 10.1002/1873-3468.70052
Lidia Itzel Castro-Rodríguez, Cristina Velez-delValle, Claudia Patricia Hernández-Mosqueira, Walid Kuri-Harcuch
{"title":"Spot-14 and its paralog Spot-14R regulate expression of metabolic and thermogenic pathway genes in murine brown and beige adipocytes","authors":"Lidia Itzel Castro-Rodríguez,&nbsp;Cristina Velez-delValle,&nbsp;Claudia Patricia Hernández-Mosqueira,&nbsp;Walid Kuri-Harcuch","doi":"10.1002/1873-3468.70052","DOIUrl":"10.1002/1873-3468.70052","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>Spot 14 (S14), encoded by <i>Thrsp</i>, is a thyroid hormone-responsive transcriptional activator that regulates lipogenesis, though its mechanisms remain unclear. We aimed to study the role of S14 on gene expression in adipocytes. We analyzed <i>Thrsp</i> and its paralog <i>Mid1ip1</i> in brown (EB5), beige (EB7), and white (F442A) adipocytes. <i>Thrsp</i> expression was higher in EB5 and EB7 than in F442A and increased with thyroid hormone T3 in EB5 and EB7 but decreased in F442A. <i>Mid1ip1</i> expression rose moderately in EB5 and EB7, influencing lipid metabolism genes. Silencing <i>Thrsp</i> upregulated <i>Mid1ip1</i> in EB7 and reduced thermogenic gene expression in EB5 and EB7. These findings underscore the roles of <i>Thrsp</i> and <i>Mid1ip1</i> in metabolic and thermogenic pathways, highlighting the responsiveness of S14 to thyroid hormones and nutrient signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 \u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>This study reveals that Thyroid Hormone-Induced Protein 8 (THRSP), also known as Spot-14, and its paralog Spot-14R, regulate metabolic and thermogenic gene expression differently in brown and beige adipocytes. These findings provide insights into adipocyte metabolism, offering potential targets for obesity and metabolic disorder treatments.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 12","pages":"1760-1780"},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interaction vesicles as emerging mediators of host-pathogen molecular crosstalk and their implications for infection dynamics. 相互作用囊泡作为宿主-病原体分子串扰的新介质及其对感染动力学的影响。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-01 DOI: 10.1002/1873-3468.70055
Bruna Sabatke, Izadora Volpato Rossi, Marcel I Ramirez
{"title":"Interaction vesicles as emerging mediators of host-pathogen molecular crosstalk and their implications for infection dynamics.","authors":"Bruna Sabatke, Izadora Volpato Rossi, Marcel I Ramirez","doi":"10.1002/1873-3468.70055","DOIUrl":"https://doi.org/10.1002/1873-3468.70055","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are critical in cell communication, transfer of biomolecules, and host-pathogen interaction. A newly identified subset, \"interaction vesicles\" (iEVs), forms through host-pathogen contact, merging membrane elements from both. These iEVs may arise through multiple mechanisms, including direct cell-cell contact, membrane contact sites, uptake and repackaging of foreign EVs, and post-release fusion of EVs. These hybrid vesicles enable pathogens to modify host environments, aiding immune evasion and infection persistence. However, iEVs may also act in favor of the host, contributing to pathogen recognition and elimination. Advanced techniques, including proteomics and high-resolution microscopy, are beginning to clarify their composition and fusion. Yet, isolating these hybrid EVs remains challenging. Overcoming these barriers could enhance understanding of infection mechanisms and support diagnostic and therapeutic innovation.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A cellular system to study responses to a collision between the transcription complex and a protein-bound nick in the DNA template 一种细胞系统，用于研究转录复合体和DNA模板中蛋白质结合缺口之间碰撞的反应。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-01 DOI: 10.1002/1873-3468.70053
Petra Herring, Morten Roedgaard, Camilla Myrup Holst, Helene Christensen, Birgitta R. Knudsen, Lotte Bjergbaek, Anni Hangaard Andersen
{"title":"A cellular system to study responses to a collision between the transcription complex and a protein-bound nick in the DNA template","authors":"Petra Herring,&nbsp;Morten Roedgaard,&nbsp;Camilla Myrup Holst,&nbsp;Helene Christensen,&nbsp;Birgitta R. Knudsen,&nbsp;Lotte Bjergbaek,&nbsp;Anni Hangaard Andersen","doi":"10.1002/1873-3468.70053","DOIUrl":"10.1002/1873-3468.70053","url":null,"abstract":"<p>We present a transcription-coupled Flp-nick system enabling a stable protein-bound nick mimicking a topoisomerase I–DNA cleavage complex. The nick is introduced at a single site within a controllable <i>LacZ</i> gene inserted into the <i>Saccharomyces cerevisiae</i> genome. This system allows unique single-site studies of a frequently occurring damage within a transcription unit <i>in vivo</i>. As proof of principle, we demonstrate RNA polymerase II accumulation at the damage site when MG132 inhibits the proteasome. Similarly, accumulation occurs when polymerase ubiquitination is abolished by deletion of the ubiquitinase <i>ELC1</i> gene. This indicates that a topoisomerase I–DNA mimicking cleavage complex <i>per se</i> induces RNA polymerase II ubiquitination and degradation. These findings advance understanding of cellular responses to topoisomerase I-targeting drugs used in cancer chemotherapy.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 12","pages":"1749-1759"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
STAT3 expression is reduced in cardiac pericytes in HFpEF and its loss reduces cellular adhesion and induces pericyte senescence HFpEF患者心脏周细胞中STAT3的表达降低，STAT3的缺失降低了细胞粘附，诱导周细胞衰老。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-01 DOI: 10.1002/1873-3468.70057
Leah Rebecca Vanicek, Ariane Fischer, Mariano Ruz Jurado, Anita Tamiato, Tara Procida-Kowalski, Jochen Wilhelm, Dennis Hecker, Maximilian Merten, Felicitas Escher, Badder Kattih, Valentina Puntmann, David John, Marcel H. Schulz, Eike Nagel, Stefanie Dimmeler, Guillermo Luxán
{"title":"STAT3 expression is reduced in cardiac pericytes in HFpEF and its loss reduces cellular adhesion and induces pericyte senescence","authors":"Leah Rebecca Vanicek,&nbsp;Ariane Fischer,&nbsp;Mariano Ruz Jurado,&nbsp;Anita Tamiato,&nbsp;Tara Procida-Kowalski,&nbsp;Jochen Wilhelm,&nbsp;Dennis Hecker,&nbsp;Maximilian Merten,&nbsp;Felicitas Escher,&nbsp;Badder Kattih,&nbsp;Valentina Puntmann,&nbsp;David John,&nbsp;Marcel H. Schulz,&nbsp;Eike Nagel,&nbsp;Stefanie Dimmeler,&nbsp;Guillermo Luxán","doi":"10.1002/1873-3468.70057","DOIUrl":"10.1002/1873-3468.70057","url":null,"abstract":"<p>Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases and is characterised by reduced pericyte coverage. While the contributions of other cardiac cell types to HFpEF are well-studied, the role of pericytes remains less understood. Using murine single-nucleus RNA-sequencing to study cardiac pericytes in HFpEF, we identified reduced <i>STAT3</i> expression as a hallmark of HFpEF pericytes. Mechanistic studies <i>in vitro</i> revealed that <i>STAT3</i> deletion induces cellular senescence and impairs pericyte adhesion, recapitulating HFpEF-like characteristics. These findings suggest that <i>STAT3</i> is crucial for maintaining pericyte homeostasis and highlight its reduction as a potential driver of pericyte loss, a defining feature of HFpEF.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 12","pages":"1781-1794"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cytoplasmic delivery of antibodies through grafting a functional single complementarity-determining region loop 通过接枝功能单一互补决定区环的细胞质递送抗体。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-05-01 DOI: 10.1002/1873-3468.70058
Yerin Jeon, Juho Choi, Youngin Roh, Eunbin Lee, Luigie Villamante, Myung-Hee Kwon
{"title":"Cytoplasmic delivery of antibodies through grafting a functional single complementarity-determining region loop","authors":"Yerin Jeon,&nbsp;Juho Choi,&nbsp;Youngin Roh,&nbsp;Eunbin Lee,&nbsp;Luigie Villamante,&nbsp;Myung-Hee Kwon","doi":"10.1002/1873-3468.70058","DOIUrl":"10.1002/1873-3468.70058","url":null,"abstract":"<p>The mouse 3D8 anti-DNA antibody can enter cells and localize in the cytoplasm, primarily facilitated by the complementarity-determining region 1 of the variable light chain (CDR L1) domain. In this study, we grafted the CDR L1 loop from 3D8 onto non-cell-penetrating IgG antibodies to investigate whether these IgGs could acquire cytoplasmic localization ability while retaining antigen-binding activity. One of three IgGs was successfully delivered into the cytoplasm while maintaining antigen-binding activity. <i>In silico</i> protein modeling suggests that this capability is linked to structural similarity between CDR L1 in the grafted Ab and that in 3D8. This study proposes a strategy to confer cell-penetrating capability by incorporating a specific CDR loop into an antibody backbone while retaining affinity.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 10","pages":"1442-1455"},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structure and stability of phycocyanin from thermotolerant Oscillatoria 耐高温振荡藻蓝蛋白的结构与稳定性。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-04-29 DOI: 10.1002/1873-3468.70048
Stuti N. Patel, Ravi R. Sonani, Gagan D. Gupta, Niraj Kumar Singh, Chandni Upadhyaya, Bhargavi Sonavane, Seema Amin, Vinay Kumar, Datta Madamwar
{"title":"Structure and stability of phycocyanin from thermotolerant Oscillatoria","authors":"Stuti N. Patel,&nbsp;Ravi R. Sonani,&nbsp;Gagan D. Gupta,&nbsp;Niraj Kumar Singh,&nbsp;Chandni Upadhyaya,&nbsp;Bhargavi Sonavane,&nbsp;Seema Amin,&nbsp;Vinay Kumar,&nbsp;Datta Madamwar","doi":"10.1002/1873-3468.70048","DOIUrl":"10.1002/1873-3468.70048","url":null,"abstract":"<p>Phycocyanin (PC), a pigment–protein complex with diverse biotechnological applications, plays a key role in light energy transfer for photosynthesis in cyanobacteria. PC (O-PC) from a thermotolerant cyanobacteria <i>Oscillatoria</i> sp. N09DM exhibits remarkable stability compared to its mesophilic counterparts, making it highly valuable for industrial and medical applications. To understand the basis of its stability, the crystal structure of O-PC is solved and analysed. Structural analysis reveals a key molecular interaction, including hydrogen bonds, salt bridges and hydrophobic interactions, along with amino acid substitutions that provide the thermal stability. Additionally, structural results provide insights into chromophore-protein interactions for understanding O-PC's role in the efficient transfer of light energy.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 10","pages":"1420-1432"},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Agrin/Dok-7-induced JPH2 phosphorylation in muscle cells is involved in AChR clustering. 肌细胞中Agrin/ dok -7诱导的JPH2磷酸化参与AChR聚集。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-04-28 DOI: 10.1002/1873-3468.70050
Beibei Wang, Mengge Cui, Huan Liu, Ming Sui, Xueyan Wu, Yu Liu, Bin Zhang
{"title":"Agrin/Dok-7-induced JPH2 phosphorylation in muscle cells is involved in AChR clustering.","authors":"Beibei Wang, Mengge Cui, Huan Liu, Ming Sui, Xueyan Wu, Yu Liu, Bin Zhang","doi":"10.1002/1873-3468.70050","DOIUrl":"https://doi.org/10.1002/1873-3468.70050","url":null,"abstract":"<p><p>The neuromuscular junction (NMJ) performs the crucial function of controlling skeletal muscle contraction. NMJ formation depends on the Agrin/Lrp4/MuSK/Dok-7 signaling pathway. However, signaling downstream of Dok-7 remains incompletely understood. Here we used the phosphorylated iTRAQ technique to identify downstream molecules of Dok-7 in muscle cells. We found 16 Agrin/Dok-7-mediated serine/threonine phosphorylated proteins, and we validated the role of one phosphorylated protein, JPH2, in regulating AChR clustering. Our phosphoproteomics analysis sheds light on the underappreciated signaling network downstream of Agrin/Dok-7, thus providing new clues for understanding pathogenesis and developing treatment methods for neuromuscular diseases.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
miRNA-29 regulates epidermal and mesenchymal functions in skin repair miRNA-29在皮肤修复中调节表皮和间充质功能。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-04-25 DOI: 10.1002/1873-3468.70051
Lalitha Thiagarajan, Rosa Sanchez-Alvarez, Chiho Kambara, Poojitha Rajasekar, Yuluang Wang, François Halloy, Jonathan Hall, Hans-Jürgen Stark, Iris Martin, Petra Boukamp, Svitlana Kurinna
{"title":"miRNA-29 regulates epidermal and mesenchymal functions in skin repair","authors":"Lalitha Thiagarajan,&nbsp;Rosa Sanchez-Alvarez,&nbsp;Chiho Kambara,&nbsp;Poojitha Rajasekar,&nbsp;Yuluang Wang,&nbsp;François Halloy,&nbsp;Jonathan Hall,&nbsp;Hans-Jürgen Stark,&nbsp;Iris Martin,&nbsp;Petra Boukamp,&nbsp;Svitlana Kurinna","doi":"10.1002/1873-3468.70051","DOIUrl":"10.1002/1873-3468.70051","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>MicroRNAs (miRNAs) control organogenesis in mammals by inhibiting translation of mRNA. Skin is an excellent model to study the role of miRNAs in epidermis and the mesenchyme. Previous research demonstrated miRNA-29 family functions in skin; however, the mRNA targets and the downstream mechanisms of miRNA-29-mediated regulation are missing. We used the miRNA crosslinking and immunoprecipitation method to find direct targets of miRNA-29 in keratinocytes and fibroblasts from human skin. miRNA-29 inhibition using modified antisense oligonucleotides in 2D and 3D cultures of keratinocytes and fibroblasts enhanced cell-to-matrix adhesion through autocrine and paracrine mechanisms of miRNA-29-dependent tissue growth. We reveal a full transcriptome of human keratinocytes with enhanced adhesion to the matrix, which supports regeneration of the epidermis and is regulated by miRNA-29.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 \u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>The functions of small, therapeutically targetable microRNA molecules identified in our study can provide a new approach to improve wound healing by restoring and enhancing the inner molecular mechanisms of a cell and its surrounding matrix. We also provide a plethora of new mRNA targets for follow-up studies of cell adhesion and extracellular matrix formation in humans.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 12","pages":"1795-1817"},"PeriodicalIF":3.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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