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Insertion of the FeB cofactor in cNORs lacking metal inserting chaperones 在缺乏金属插入伴侣的cnor中插入FeB辅助因子。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-10 DOI: 10.1002/1873-3468.70007
Sofia Appelgren, Pia Ädelroth
{"title":"Insertion of the FeB cofactor in cNORs lacking metal inserting chaperones","authors":"Sofia Appelgren,&nbsp;Pia Ädelroth","doi":"10.1002/1873-3468.70007","DOIUrl":"10.1002/1873-3468.70007","url":null,"abstract":"<p>Cytochrome <i>c</i>-dependent nitric oxide reductase (<i>c</i>NOR) catalyzes the reduction of NO into nitrous oxide (N<sub>2</sub>O), a strong greenhouse gas released from denitrifying microorganisms. The <i>c</i>NOR active site holds an essential non-heme iron, Fe<sub>B</sub>, inserted using the chaperone complex NorQD. However, in <i>Thermus thermophilus</i>, the <i>c</i>NOR (<i>Ttc</i>NOR) cluster lacks the <i>norQD</i> genes. Here we investigated Fe<sub>B</sub> insertion into <i>Ttc</i>NOR and characterized and compared <i>Ttc</i>NOR expressed in <i>Escherichia coli</i> to that natively produced. We show that Fe<sub>B</sub> is present in the natively produced <i>Ttc</i>NOR only. Analysis of <i>c</i>NOR operon sequences suggests that a hydrophilic K-pathway analogue is present in <i>c</i>NORs that do not rely on NorQD for iron insertion. We discuss the implications of our data for the evolution of the NOR family.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 9","pages":"1269-1284"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382043","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
The apo LETM1 F-EF-hand adopts a closed conformation that underlies a multi-modal sensory role in mitochondria 载脂蛋白LETM1 F-EF-hand采用封闭构象，是线粒体中多模态感觉作用的基础。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-10 DOI: 10.1002/1873-3468.70006
Qi-Tong Lin, Danielle M. Colussi, Peter B. Stathopulos
{"title":"The apo LETM1 F-EF-hand adopts a closed conformation that underlies a multi-modal sensory role in mitochondria","authors":"Qi-Tong Lin,&nbsp;Danielle M. Colussi,&nbsp;Peter B. Stathopulos","doi":"10.1002/1873-3468.70006","DOIUrl":"10.1002/1873-3468.70006","url":null,"abstract":"<p>Leucine zipper EF-hand containing transmembrane protein-1 (LETM1) plays a critical role in mitochondrial function, with haploinsufficiency linked to Wolf-Hirschhorn syndrome. Here, we present the solution NMR structure of the calcium (Ca<sup>2+</sup>)-depleted LETM1 EF-hand domain, revealing a closed conformation facilitated by a distinct F<sub>1</sub>-helix pivot rather than decreased interhelical angle. Further, we observe regiospecific unfolding in response to hot and cold denaturation and show H662 has a pKa in-line with physiological pH fluctuations. Finally, we demonstrate Ca<sup>2+</sup>-dependent transient interactions between the EF-hand and other LETM1 or GHITM protein domains. Collectively, our data reveal the apo-to-holo structural dynamics and mechanisms underlying the multi-modal sensing by the LETM1 EF-hand domain, highlighting its role as an adaptable regulatory element within the mitochondrial matrix.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 7","pages":"971-988"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382046","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
Integrated interactome, proteomic and functional analyses reveal molecular pathways driving L1TD1-induced aggressiveness in CNS embryonal tumor cells 综合相互作用组学、蛋白质组学和功能分析揭示了驱动l1td1诱导的中枢神经系统胚胎肿瘤细胞侵袭性的分子途径。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-06 DOI: 10.1002/1873-3468.70002
Thiago Giove Mitsugi, Matt Sherwood, Elisa Helena Farias Jandrey, Amanda Faria Assoni, Joseph Bell, Brandon Coke, Paul Skipp, Rob Ewing, Oswaldo Keith Okamoto
{"title":"Integrated interactome, proteomic and functional analyses reveal molecular pathways driving L1TD1-induced aggressiveness in CNS embryonal tumor cells","authors":"Thiago Giove Mitsugi,&nbsp;Matt Sherwood,&nbsp;Elisa Helena Farias Jandrey,&nbsp;Amanda Faria Assoni,&nbsp;Joseph Bell,&nbsp;Brandon Coke,&nbsp;Paul Skipp,&nbsp;Rob Ewing,&nbsp;Oswaldo Keith Okamoto","doi":"10.1002/1873-3468.70002","DOIUrl":"10.1002/1873-3468.70002","url":null,"abstract":"<p>L1TD1 is a pluripotency factor required for embryonic stem cell self-renewal; its expression has also been detected in solid tumors, including embryonal tumors of the central nervous system (CNS). Previously, we showed that L1TD1 expression correlates with metastasis formation and shorter overall survival of medulloblastoma patients. Here, we used affinity purification coupled to mass spectrometry to map the L1TD1 interactome, and global proteomics to assess proteins differentially regulated by L1TD1 expression in patient-derived embryonal CNS tumor cell lines. We identified novel L1TD1 interactors and differentially expressed proteins related to cell proliferation, death and motility. Finally, we demonstrated that L1TD1-overexpressing tumor cells have distinct cell morphology with enhanced filopodial formation, higher cell motility, greater proliferation capability, and reduced sensitivity to cisplatin treatment.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 7","pages":"1029-1045"},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255300","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
The Lily Foundation: supporting patients, raising awareness and funding research into mitochondrial diseases 百合基金会：支持患者，提高认识，资助线粒体疾病的研究。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-06 DOI: 10.1002/1873-3468.15107
Liz Curtis, Maria E. O'Hanlon, Katie Waller, Duncan E. Wright
{"title":"The Lily Foundation: supporting patients, raising awareness and funding research into mitochondrial diseases","authors":"Liz Curtis,&nbsp;Maria E. O'Hanlon,&nbsp;Katie Waller,&nbsp;Duncan E. Wright","doi":"10.1002/1873-3468.15107","DOIUrl":"10.1002/1873-3468.15107","url":null,"abstract":"<p>Primary mitochondrial diseases (‘mito’) are a group of genetically and phenotypically diverse disorders caused by defects in mitochondrial structure or function. Although they are individually rare, they collectively have an incidence of around 1 : 4300. Mitochondrial diseases can arise from mutations in either mitochondrial or nuclear genes, complicating genetic diagnosis. The Lily Foundation was founded by Liz Curtis in the UK in 2007 in order to raise awareness of mitochondrial diseases and to fund research into diagnosis and treatment. In this first of a new series on patient advocacy, <i>FEBS Letters</i> interviews Founder and CEO Liz Curtis MBE, Head of Patient Programmes Katie Waller and Research Manager Dr. Maria O'Hanlon on the aims, achievements and activities of the Lily Foundation.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 4","pages":"459-465"},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255302","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
Functional variation among LPMOs revealed by the inhibitory effects of cyanide and buffer ions 氰化物和缓冲离子的抑制作用揭示了LPMOs之间的功能差异。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-06 DOI: 10.1002/1873-3468.15105
Ole Golten, Lorenz Schwaiger, Zarah Forsberg, Kelsi R. Hall, Anton A. Stepnov, Tom Z. Emrich-Mills, Iván Ayuso-Fernández, Morten Sørlie, Roland Ludwig, Åsmund Kjendseth Røhr, Vincent G. H. Eijsink
{"title":"Functional variation among LPMOs revealed by the inhibitory effects of cyanide and buffer ions","authors":"Ole Golten,&nbsp;Lorenz Schwaiger,&nbsp;Zarah Forsberg,&nbsp;Kelsi R. Hall,&nbsp;Anton A. Stepnov,&nbsp;Tom Z. Emrich-Mills,&nbsp;Iván Ayuso-Fernández,&nbsp;Morten Sørlie,&nbsp;Roland Ludwig,&nbsp;Åsmund Kjendseth Røhr,&nbsp;Vincent G. H. Eijsink","doi":"10.1002/1873-3468.15105","DOIUrl":"10.1002/1873-3468.15105","url":null,"abstract":"<p>Enzymes known as lytic polysaccharide monooxygenases (LPMOs) are mono-copper polysaccharide-degrading peroxygenases that engage in several on- and off-pathway redox reactions involving O<sub>2</sub> and H<sub>2</sub>O<sub>2</sub>. Herein, we show that the known metalloenzyme inhibitor cyanide inhibits reductive activation of LPMOs by binding to the LPMO-Cu(II) state and that the degree of inhibition depends on the concentrations of the polysaccharide substrate, the reductant and H<sub>2</sub>O<sub>2</sub>. Importantly, this analysis revealed differences between fungal <i>Nc</i>AA9C and bacterial <i>Sm</i>AA10A, which have different secondary copper coordination spheres. These differences were also highlighted by the observation that phosphate, a commonly used buffer ion, strongly inhibits <i>Nc</i>AA9C while not affecting reactions with <i>Sm</i>AA10A. The results provide insight into LPMO inhibition and catalysis and highlight pitfalls in the analysis thereof.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 9","pages":"1317-1336"},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255298","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
Inclusion, belonging, and institutional climate – overlooked factors driving diverse STEM faculty turnover? 包容、归属感和制度氛围——被忽视的推动STEM教师多样化流动的因素？
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-06 DOI: 10.1002/1873-3468.70005
Mali D. Doles, Joseph T. Cornelius, Jason D. Doles
{"title":"Inclusion, belonging, and institutional climate – overlooked factors driving diverse STEM faculty turnover?","authors":"Mali D. Doles,&nbsp;Joseph T. Cornelius,&nbsp;Jason D. Doles","doi":"10.1002/1873-3468.70005","DOIUrl":"10.1002/1873-3468.70005","url":null,"abstract":"<p>Faculty turnover at institutes of higher learning disrupts educational continuity, compromises scholarly activity, has negative impacts on learner experiences, and is costly. As such, understanding the reasons why faculty leave—especially in cases where they plan to stay in academia—is critically important with respect to designing and implementing informed retention initiatives. We conducted a survey of STEM faculty who recently switched institutions to gain insights into factors driving their decision to leave. Across all respondents, we found that factors relating to culture/climate were more important than factors relating to pay/compensation or position title. This relative prioritization was even more apparent among women faculty and faculty from disadvantaged backgrounds. We contextualize and discuss the implications of our findings and provide strategies for cultivating inclusive climates to promote faculty retention.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 6","pages":"791-798"},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364159","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
IL-6 mediated CD206+ARG-1+ tumor associated macrophage polarization induces Treg infiltration in non-responder luminal A breast cancer IL-6介导的CD206+ARG-1+肿瘤相关巨噬细胞极化诱导无应答腔A乳腺癌Treg浸润。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-04 DOI: 10.1002/1873-3468.70000
Ananya Das, Sraddhya Roy, Aparajita Bairagi, Neyaz Alam, Nabanita Chatterjee
{"title":"IL-6 mediated CD206+ARG-1+ tumor associated macrophage polarization induces Treg infiltration in non-responder luminal A breast cancer","authors":"Ananya Das,&nbsp;Sraddhya Roy,&nbsp;Aparajita Bairagi,&nbsp;Neyaz Alam,&nbsp;Nabanita Chatterjee","doi":"10.1002/1873-3468.70000","DOIUrl":"10.1002/1873-3468.70000","url":null,"abstract":"<p>Drug non-responsiveness is the major reason for the poor prognosis of hormonal receptor-positive breast cancer (ER<sup>+</sup>/PR<sup>+</sup> BCa), particularly the luminal A subtype. However, the underlying mechanism of drug non-responsiveness remains unknown. Flow cytometry and t-SNE analysis followed by ELISA validation of responder and non-responder unveiled lower secretion of IFN-γ, IL-12, and higher levels of IL-6 and TGF-β in CD4<sup>+</sup> T cells (<i>P</i> &lt; 0.001), CD8<sup>+</sup> T cells (<i>P</i> &lt; 0.001), FOXP3<sup>+</sup> Tregs (<i>P</i> &lt; 0.001) and CD206<sup>+</sup> TAMs (<i>P</i> &lt; 0.001) in non-responders. Treatment of isolated CD206<sup>+</sup> TAMs with recombinant IL-6 upregulated the expression of ARG-1 (arginase-1) and subsequent increase of TGF-β<sup>+</sup> Tregs (<i>P</i> &lt; 0.001) and IL-6<sup>+</sup> Tregs (<i>P</i> &lt; 0.001) in luminal A BCa. Our findings showed IL-6 mediated ARG-1<sup>+</sup>CD206<sup>+</sup> TAMs polarization induced FOXP3<sup>+</sup> Tregs infiltration in TME of non-responder in luminal A BCa.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 5","pages":"739-754"},"PeriodicalIF":3.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188688","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
Insight into the function of the Golgi membrane protein GOLM1 in cholangiocytes through interactomic analysis 通过相互作用分析了解高尔基膜蛋白GOLM1在胆管细胞中的功能。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-02-01 DOI: 10.1002/1873-3468.70001
Meghana Nagaraj, Sharath Kumar Goud Emmagouni, Vaishali Chaurasiya, Luyang Li, Van Dien Nguyen, Salla Keskitalo, Markku Varjosalo, You Zhou, P. A. Nidhina Haridas, Vesa M. Olkkonen
{"title":"Insight into the function of the Golgi membrane protein GOLM1 in cholangiocytes through interactomic analysis","authors":"Meghana Nagaraj,&nbsp;Sharath Kumar Goud Emmagouni,&nbsp;Vaishali Chaurasiya,&nbsp;Luyang Li,&nbsp;Van Dien Nguyen,&nbsp;Salla Keskitalo,&nbsp;Markku Varjosalo,&nbsp;You Zhou,&nbsp;P. A. Nidhina Haridas,&nbsp;Vesa M. Olkkonen","doi":"10.1002/1873-3468.70001","DOIUrl":"10.1002/1873-3468.70001","url":null,"abstract":"<p>GOLM1, a Golgi membrane protein, is upregulated in cancers and liver diseases. Analysis of public RNAseq data from healthy human liver suggested that GOLM1 is predominantly expressed in cholangiocytes. Therefore, this study was initiated to understand the molecular functions of GOLM1 in cholangiocytes through protein interactomics. The findings reveal a number of putative GOLM1-interacting partners involved in cellular regimes such as mitochondrial and Golgi functions, ribonucleoprotein biogenesis, cell cycle, and basement membrane organization. Further, to validate select key roles, GOLM1 was silenced in MMNK-1 cholangiocytes and the effects on cell functions were studied. The silencing resulted in impaired mitochondrial function, reduced mitochondrial and P-body markers, increased apoptosis, and reduced cell adhesion, suggesting crucial roles of GOLM1 in maintaining normal cholangiocyte metabolism and function.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 9","pages":"1299-1316"},"PeriodicalIF":3.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074124","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
Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases Kelch结构域（KLHDC）亚家族的特征及其与疾病的关系
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-30 DOI: 10.1002/1873-3468.15108
Courtney Pilcher, Paula Armina V. Buco, Jia Q. Truong, Paul A. Ramsland, Monique F. Smeets, Carl R. Walkley, Jessica K. Holien
{"title":"Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases","authors":"Courtney Pilcher,&nbsp;Paula Armina V. Buco,&nbsp;Jia Q. Truong,&nbsp;Paul A. Ramsland,&nbsp;Monique F. Smeets,&nbsp;Carl R. Walkley,&nbsp;Jessica K. Holien","doi":"10.1002/1873-3468.15108","DOIUrl":"10.1002/1873-3468.15108","url":null,"abstract":"<p>The Kelch protein superfamily is an evolutionary conserved family containing 63 alternate protein coding members. The superfamily is split into three subfamilies: Kelch like (KLHL), Kelch-repeat and bric-a-bracs (BTB) domain containing (KBTBD) and Kelch domain containing protein (KLHDC). The KLHDC subfamily is one of the smallest within the Kelch superfamily, containing 10 primary members. There is little known about the structures and functions of the subfamily; however, they are thought to be involved in several cellular and molecular processes. Recently, there have been significant structural and biochemical advances for KLHDC2, which has aided our understanding of other KLHDC family members. Furthermore, small molecules directly targeting KLHDC2 have been identified, which act as tools for targeted protein degradation. This review utilises this information, in conjunction with a thorough exploration of the structural aspects and potential biological functions to summarise the relationship between KLHDCs and human disease.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1094-1112"},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064707","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
Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury 消融α -平滑肌肌动蛋白表达细胞中的LRP6可消除博莱霉素诱导的肺损伤后的肺部炎症和纤维化。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-28 DOI: 10.1002/1873-3468.15106
Eun-Ah Sung, Mikhail G. Dozmorov, SuJeong Song, Theingi Aung, Min Hee Park, Patricia J. Sime, Wook-Jin Chae
{"title":"Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury","authors":"Eun-Ah Sung,&nbsp;Mikhail G. Dozmorov,&nbsp;SuJeong Song,&nbsp;Theingi Aung,&nbsp;Min Hee Park,&nbsp;Patricia J. Sime,&nbsp;Wook-Jin Chae","doi":"10.1002/1873-3468.15106","DOIUrl":"10.1002/1873-3468.15106","url":null,"abstract":"<p>Tissue fibrosis is a progressive pathological process with excessive deposition of extracellular matrix proteins (ECM). Myofibroblasts, identified by alpha-smooth muscle actin (αSMA) expression, play an important role in tissue fibrosis by producing ECM. Here, we found that the Wnt antagonist Dickkopf1 (DKK1) induced gene expressions associated with inflammation and fibrosis in lung fibroblasts. We demonstrated that genetic deletion of LRP6, a receptor for Wnt ligands and DKK1, in αSMA-expressing cells using Acta2-cre <i>Lrp6</i><sup>fl/fl</sup> (<i>Lrp6</i><sup>AKO</sup>) mice abrogated the bleomycin (BLM)-induced lung inflammation and fibrosis phenotype, suggesting an important role for LRP6 in modulating inflammation and fibrotic processes in the lung. Our results highlight the crucial role of LRP6 in fibroblasts in regulating inflammation and fibrosis upon BLM-induced lung injury.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 10","pages":"1468-1480"},"PeriodicalIF":3.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052115","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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