Biochimica et biophysica acta. Molecular cell research最新文献

{"title":"Targeting SOCS2 alleviates myocardial fibrosis by reducing nuclear translocation of β-catenin","authors":"Ming Yuan ,&nbsp;Hongjie Shi ,&nbsp;Bin Wang ,&nbsp;Jie Cai ,&nbsp;Wenjun Yu ,&nbsp;Wei Wang ,&nbsp;Qiaofeng Qian ,&nbsp;Yumou Wang ,&nbsp;Xianwu Zhou ,&nbsp;Jinping Liu","doi":"10.1016/j.bbamcr.2024.119804","DOIUrl":"10.1016/j.bbamcr.2024.119804","url":null,"abstract":"<div><h3>Background</h3><p>Myocardial fibrosis is an important pathological feature of dilated cardiomyopathy (DCM). The roles of SOCS2 in fibrosis of different organs are controversial. Herein, we investigated the function and potential mechanism of SOCS2 in myocardial fibrosis.</p></div><div><h3>Methods</h3><p>Bioinformatics, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), real-time fluorescence quantitative PCR (qPCR), rat primary myocardial fibroblasts (rCFs) culture, doxorubicin (DOX) induced mouse dilated cardiomyopathy (DCM) model, and in vivo adeno-associated virus (AAV) infection were used to explore the role of SOCS2 in DCM.</p></div><div><h3>Results</h3><p>Bioinformatics analysis showed that SOCS2 was positively correlated with fibrosis related factors. SOCS2 was significantly upregulated in patients and mice with DCM. In vivo experiments showed that targeted inhibition of cardiac SOCS2 could improve mouse cardiac function and alleviate myocardial fibrosis. Further research demonstrated that SOCS2 promoted the transformation of myofibroblasts. Knockdown of SOCS2 reduced the nuclear localization of β-catenin, which inhibited the fibrogenic effect of Wnt/β-catenin pathway. In addition, bioinformatics analysis suggested that lymphoid enhancer binding factor 1 (LEF1) was significantly positively correlated with SOCS2. Finally, dual luciferase assays demonstrated that LEF1 could bind to the promoter region of SOCS2, thereby mediating its transcriptional activation.</p></div><div><h3>Conclusion</h3><p>SOCS2 could activate the Wnt/β-catenin by regulating the nuclear translocation of β-catenin, which induces the transcriptional activation of SOCS2. Overall, these results indicated a positive feedback activation phenomenon between SOCS2, β-catenin and LEF1 in DCM. These results suggested that inhibition of SOCS2 could effectively alleviate the progression of myocardial fibrosis and improve cardiac function.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119804"},"PeriodicalIF":4.6,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircSlc17a5 controlled by VLDLR/QKI pathway regulated the choroidal angiogenesis","authors":"Fang Deng,&nbsp;Chong-Bo Chen,&nbsp;Huiping Li,&nbsp;Shaofen Huang,&nbsp;Ciyan Xu,&nbsp;Xiaoqiang Xiao","doi":"10.1016/j.bbamcr.2024.119802","DOIUrl":"10.1016/j.bbamcr.2024.119802","url":null,"abstract":"<div><h3>Rationale</h3><p>Very-low-density lipoprotein receptor (VLDLR) involves in ocular neovascularization, a major cause of severe vision loss. However, the underlying molecular mechanisms were not completely clarified. Here, we aimed to investigate roles of circular RNAs (circRNAs) in VLDLR-associated ocular neovascularization.</p></div><div><h3>Methods</h3><p><em>Vldlr</em> knockout (<em>Vldlr</em>-/-, ko), <em>Robo4</em> knockout (<em>Robo4</em>-/-, ko) and wild-type (WT) mice were used. Mouse model of oxygen induced retinopathy (OIR) and high-throughput sequence were performed to profile the differential expression of circRNA and transcripts. RNase R treatment, Sanger PCR sequencing and quantitative polymerase chain reaction (qPCR) were used to validate candidate circRNAs and their expression patterns. Choroidal sprouting assay ex vivo and laser induction choroid neovascularization were used to determine the expression and functions of QKI/CircSlc17a5 on choroidal neovascularization.</p></div><div><h3>Results</h3><p>In macrophage and ocular tissues derived from <em>Vldlr</em> (<em>Vldlr-/-,Vldlr ko</em>) or <em>Robo4</em> (<em>Robo4-/-,Robo4 ko</em>) deficiency as well as wild-type (WT) mice, Quaking (<em>Qki)</em> expression was significantly down-regulated in <em>Vldlr</em> deficiency compared to WT and <em>Robo4</em> deficiency groups. Ectopic VLDLR expression or Reelin stimulation increased expression of QKI in bEnd.3 cells. Circular RNA sequencing uncovered that VLDLR regulated the biogenesis of certain circular RNAs, including the circSlc17a5. The number of Circular RNAs increased in mice treated with OIR. QKI mediated the biogenesis of circSlc17a5, which was an important regulator of choroidal angiogenesis.</p></div><div><h3>Conclusion</h3><p>CircSlc17a5 regulated by VLDLR/QKI plays important roles in the choroidal angiogenesis.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119802"},"PeriodicalIF":4.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001459/pdfft?md5=20b99ccf404544a7cfb7423752401259&pid=1-s2.0-S0167488924001459-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythropoietin enhances iron bioavailability in HepG2 cells by downregulating hepcidin through mTOR, C/EBPα and HIF-1α","authors":"Romina Eugenia Maltaneri,&nbsp;María Eugenia Chamorro,&nbsp;Silvana Estela Gionco,&nbsp;Alcira Beatriz Nesse,&nbsp;Daniela Cecilia Vittori","doi":"10.1016/j.bbamcr.2024.119800","DOIUrl":"10.1016/j.bbamcr.2024.119800","url":null,"abstract":"<div><p>The regulation of iron (Fe) levels is essential to maintain an adequate supply for erythropoiesis, among other processes, and to avoid possible toxicity. The liver-produced peptide hepcidin is regarded as the main regulator of Fe absorption in enterocytes and release from hepatocytes and macrophages, as it impairs Fe export through ferroportin. The glycoprotein erythropoietin (Epo) drives erythroid progenitor survival and differentiation in the bone marrow, and has been linked to the mobilization of Fe reserves necessary for hemoglobin production. Herein we show that Epo inhibits hepcidin expression directly in the HepG2 hepatic cell line, thus leading to a decrease in intracellular Fe levels. Such inhibition was dependent on the Epo receptor-associated kinase JAK2, as well as on the PI3K/AKT/mTOR pathway, which regulates nutrient homeostasis. Epo was also found to decrease binding of the C/EBP-α transcription factor to the hepcidin promoter, which could be attributed to an increased expression of its inhibitor CHOP. Epo did not only hinder the stimulating effect of C/EBP-α on hepcidin transcription, but also favored hepcidin inhibition by HIF-1α, by increasing is nuclear translocation as well as its protein levels. Moreover, in assays with the inhibitor genistein, this transcription factor was found necessary for Epo-induced hepcidin suppression. Our findings support the involvement of the PI3K/AKT/mTOR pathway in the regulation of Fe levels by Epo, and highlight the contrasting roles of the C/EBP-α and HIF-1α transcription factors as downstream effectors of the cytokine in this process.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119800"},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression","authors":"Yasuo Okamoto ,&nbsp;Keisuke Kitakaze ,&nbsp;Yasuhiro Takenouchi ,&nbsp;Rena Matsui ,&nbsp;Daisuke Koga ,&nbsp;Ryo Miyashima ,&nbsp;Hironobu Ishimaru ,&nbsp;Kazuhito Tsuboi","doi":"10.1016/j.bbamcr.2024.119798","DOIUrl":"10.1016/j.bbamcr.2024.119798","url":null,"abstract":"<div><p>Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused by myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets of current antifibrotic drugs, no drug has yet been approved to stop fibrosis progression. Herein, we aimed to identify GPCRs with profibrotic effects. In gene expression analysis of mouse lungs with induced fibrosis, eight GPCRs were identified, showing a &gt;2-fold increase in mRNA expression after fibrosis induction. Among them, we focused on Gpr176 owing to its significant correlation with a myofibroblast marker α-smooth muscle actin (αSMA), the profibrotic factor transforming growth factor β1 (TGFβ1), and collagen in a human lung gene expression database. Similar to the lung fibrosis model, increased <em>Gpr176</em> expression was also observed in other organs affected by fibrosis, including the kidney, liver, and heart, suggesting its role in fibrosis across various organs. Furthermore, fibroblasts abundantly expressed Gpr176 compared to alveolar epithelial cells, endothelial cells, and macrophages in the fibrotic lung. GPR176 expression was unaffected by TGFβ1 stimulation in rat renal fibroblast NRK-49 cells, whereas knockdown of Gpr176 by siRNA reduced TGFβ1-induced expression of αSMA, fibronectin, and collagen as well as Smad2 phosphorylation. This suggested that Gpr176 regulates fibroblast activation. Consequently, Gpr176 acts in a profibrotic manner, and inhibiting its activity could potentially prevent myofibroblast differentiation and improve fibrosis. Developing a GPR176 inverse agonist or allosteric modulator is a promising therapeutic approach for fibrosis.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119798"},"PeriodicalIF":4.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001411/pdfft?md5=5af8dcb025784d23175bb8f54ffefe0e&pid=1-s2.0-S0167488924001411-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-angiogenic and anti-vasculogenic mimicry effects of GN25 in endothelial and glioma cells","authors":"Zhi-Hong Wen ,&nbsp;Long Chang ,&nbsp;San-Nan Yang ,&nbsp;Chen-Ling Yu ,&nbsp;Fang-Yu Tung ,&nbsp;Hsiao-Mei Kuo ,&nbsp;I-Chen Lu ,&nbsp;Chang-Yi Wu ,&nbsp;Po-Chang Shih ,&nbsp;Wu-Fu Chen ,&nbsp;Nan-Fu Chen","doi":"10.1016/j.bbamcr.2024.119799","DOIUrl":"10.1016/j.bbamcr.2024.119799","url":null,"abstract":"<div><h3>Background and purpose</h3><p>Scientists have been exploring anti-angiogenic strategies to inhibit angiogenesis and prevent tumor growth. Vasculogenic mimicry (VM) in glioblastoma multiforme (GBM) poses a challenge, complicating anti-angiogenesis therapy. A novel drug, GN25 (3-[{1,4-dihydro-5,8-dimethoxy-1,4-dioxo-2-naphthalenyl}thio]-propanoic acid), can inhibit tumor formation. This study aims to investigate the microenvironmental effects and molecular mechanisms of GN25 in anti-angiogenesis and anti-VM.</p></div><div><h3>Experimental approach</h3><p>MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the cell viability of different concentrations of GN25 in human umbilical vein endothelial cells (HUVEC) and Uppsala 87 malignant glioma (U87MG) cells. Functional assays were used to investigate the effects of GN25 on angiogenesis-related processes, whereas gelatin zymography, enzyme-linked immunosorbent assays, and Western blotting were utilized to assess the influence on matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) secretion and related signaling pathways.</p></div><div><h3>Key results</h3><p>GN25 suppressed migration, wound healing, and tube formation in HUVECs and disrupted angiogenesis in a rat aorta ring and zebrafish embryo model. GN25 dose-dependently reduced phosphatidylinositol 3-kinase/AKT and inhibited MMP-2/VEGF secretion in HUVECs. In U87MG cells, GN25 inhibited migration, wound healing, and VM, accompanied by a decrease in MMP-2 and VEGF secretion. The results indicate that GN25 effectively inhibits angiogenesis and VM formation in HUVECs and U87MG cells without affecting preexisting vascular structures.</p></div><div><h3>Conclusion and implications</h3><p>This study elaborated GN25's potential as an anti-angiogenic agent by elucidating its inhibitory effects on classical angiogenesis. VM provides valuable insights for developing novel therapeutic strategies against tumor progression and angiogenesis-related diseases. These results indicate the potential of GN25 as a promising candidate for angiogenesis-related diseases.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119799"},"PeriodicalIF":4.6,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetrameric, active PKM2 inhibits IP3 receptors, potentially requiring GRP75 as an additional interaction partner","authors":"Fernanda O. Lemos ,&nbsp;Ian de Ridder ,&nbsp;Larry Wagner ,&nbsp;Martin D. Bootman ,&nbsp;Geert Bultynck ,&nbsp;David I. Yule ,&nbsp;Jan B. Parys","doi":"10.1016/j.bbamcr.2024.119796","DOIUrl":"10.1016/j.bbamcr.2024.119796","url":null,"abstract":"<div><p>Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme interacting with the inositol 1,4,5-trisphosphate receptor (IP₃R). This interaction suppresses IP₃R-mediated cytosolic [Ca²⁺] rises. As PKM2 exists in monomeric, dimeric and tetrameric forms displaying different properties including catalytic activity, we investigated the molecular determinants of PKM2 enabling its interaction with IP₃Rs. Treatment of HeLa cells with TEPP-46, a compound stabilizing the tetrameric form of PKM2, increased both its catalytic activity and the suppression of IP₃R-mediated Ca²⁺ signals. Consistently, in PKM2 knock-out HeLa cells, PKM2^C424L, a tetrameric, highly active PKM2 mutant, but not inactive PKM2^K270M or the less active PKM2^K305Q, suppressed IP₃R-mediated Ca²⁺ release. Surprisingly, however, in vitro assays did not reveal a direct interaction between purified PKM2 and either the purified Fragment 5 of IP₃R1 (a.a. 1932–2216) or the therein located D5SD peptide (a.a. 2078–2098 of IP₃R1), the presumed interaction sites of PKM2 on the IP₃R. Moreover, on-nucleus patch clamp of heterologously expressed IP₃R1 in DT40 cells devoid of endogenous IP₃Rs did not reveal any functional effect of purified wild-type PKM2, mutant PKM2 or PKM1 proteins. These results indicate that an additional factor mediates the regulation of the IP₃R by PKM2 in cellulo. Immunoprecipitation of GRP75 using HeLa cell lysates co-precipitated IP₃R1, IP₃R3 and PKM2. Moreover, the D5SD peptide not only disrupted PKM2:IP₃R, but also PKM2:GRP75 and GRP75:IP₃R interactions. Our data therefore support a model in which catalytically active, tetrameric PKM2 suppresses Ca²⁺ signaling via the IP₃R through a multiprotein complex involving GRP75.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119796"},"PeriodicalIF":4.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caveolin-2 controls preadipocyte survival in the mitotic clonal expansion for adipogenesis","authors":"Moonjeong Choi ,&nbsp;Kyuho Jeong ,&nbsp;Yunbae Pak","doi":"10.1016/j.bbamcr.2024.119793","DOIUrl":"10.1016/j.bbamcr.2024.119793","url":null,"abstract":"<div><p>Here, we report that Caveolin-2 (Cav-2) is a cell cycle regulator in the mitotic clonal expansion (MCE) for adipogenesis. For the G2/M phase transition and re-entry into the G1 phase, dephosphorylated Cav-2 by protein tyrosine phosphatase 1B (PTP1B) controlled epigenetic activation of <em>Ccnb1</em>, <em>Cdk1</em>, and <em>p21</em> in a lamin A/C-dependent manner, thereby ensuring the survival of preadipocytes. Cav-2, associated with lamin A/C, recruited the repressed promoters of <em>Ccnb1</em> and <em>Cdk1</em> for activation, and disengaged the active promoter of <em>p21</em> from lamin A/C for inactivation through histone H3 modifications at the nuclear periphery. Cav-2 deficiency abrogated the histone H3 modifications and impeded the transactivation of <em>Ccnb1</em>, <em>Cdk1</em>, and <em>p21</em>, leading to a delay in mitotic entry, retardation of re-entry into G1 phase, and the apoptotic cell death of preadipocytes. Re-expression of Cav-2 restored the G2/M phase transition and G1 phase re-entry, preadipocyte survival, and adipogenesis in Cav-2-deficient preadipocytes. Our study uncovers a novel mechanism by which cell cycle transition and apoptotic cell death are controlled for adipocyte hyperplasia.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119793"},"PeriodicalIF":4.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRP1 promotes osteo/odontogenic differentiation via shroom3 in dental pulp stem cells","authors":"Zongyu Li,&nbsp;Aokang Yao,&nbsp;Xinyue Yang,&nbsp;Sheng Luo,&nbsp;Zhuoyang Wu,&nbsp;Yaqiong Yu","doi":"10.1016/j.bbamcr.2024.119795","DOIUrl":"10.1016/j.bbamcr.2024.119795","url":null,"abstract":"<div><p>Neuropilin-1 (NRP1) is a single transmembrane glycoprotein involved in a variety of physiological events. However, the exact mechanisms by which NRP1 regulates dental pulp stem cells (DPSCs) to differentiate toward an osteo/odontogenic phenotype are poorly understood. Here, we determined the significantly increased expression of full-length NRP1 and glycosaminoglycan (GAG)-modified NRP1 during osteo/odontogenesis in DPSCs. NRP1 was confirmed to promote alkaline phosphatase (ALP) activity, mineralized nodule deposition, protein and mRNA expression of Runx2, DSPP and DMP1 in DPSCs via the loss-of-function and gain-of-function approaches. Further, a non-GAG-modified NRP1 mutant (NRP1 S₆₁₂A) was generated and the suppression of osteo/odontogenic differentiation was observed in the NRP1 S₆₁₂A overexpression cells. Knockdown of the adaptor protein shroom3 resulted in the inhibition of osteo/odontogenesis. The protein-protein interaction network, the protein-protein docking and confocal analyses indicated the interactions between NRP1 and shroom3. Furthermore, immunoprecipitation followed by western analysis confirmed the binding of NRP1 to shroom3, but overexpression of NRP1 S₆₁₂A greatly influenced the recruitment of shroom3 by NRP1. These results provide strong evidence that NRP1 is a critical regulator for osteo/odontogenesis through interacting with shroom3. Moreover, our results indicate that NRP1 S₆₁₂A attenuates osteo/odontogenesis, suggesting that GAG modification is essential for NRP1 in DPSCs.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119795"},"PeriodicalIF":4.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron‑sulfur cluster synthesis in plastids by the SUF system: A mechanistic and structural perspective","authors":"Antoine Kairis ,&nbsp;Benjamin Das Neves ,&nbsp;Jérémy Couturier ,&nbsp;Claire Remacle ,&nbsp;Nicolas Rouhier","doi":"10.1016/j.bbamcr.2024.119797","DOIUrl":"10.1016/j.bbamcr.2024.119797","url":null,"abstract":"<div><p>About 50 proteins expressed in plastids of photosynthetic eukaryotes ligate iron‑sulfur (Fe-S) clusters and ensure vital functions in photosynthesis, sulfur and nitrogen assimilation, but also in the synthesis of pigments, vitamins and hormones. The synthesis of these Fe-S clusters, which are co- or post-translationally incorporated into these proteins, relies on several proteins belonging to the so-called sulfur mobilization (SUF) machinery. An Fe-S cluster is first <em>de novo</em> synthesized on a scaffold protein complex before additional late-acting maturation factors act in the specific transfer, possible conversion and insertion of this cluster into target recipient proteins. In this review, we will summarize what is known about the molecular mechanisms responsible for both the synthesis and transfer steps, focusing in particular on the structural aspects that allow the formation of the required protein complexes.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119797"},"PeriodicalIF":4.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016748892400140X/pdfft?md5=29b5a7e8c72afeb7e47322837e37384a&pid=1-s2.0-S016748892400140X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming of normal fibroblasts into ovarian cancer-associated fibroblasts via non-vesicular paracrine signaling induces an activated fibroblast phenotype","authors":"Hailey Axemaker ,&nbsp;Simona Plesselova ,&nbsp;Kristin Calar ,&nbsp;Megan Jorgensen ,&nbsp;Jared Wollman ,&nbsp;Pilar de la Puente","doi":"10.1016/j.bbamcr.2024.119801","DOIUrl":"10.1016/j.bbamcr.2024.119801","url":null,"abstract":"<div><p>Cancer-associated fibroblasts (CAFs) are key contributors to ovarian cancer (OC) progression and therapeutic resistance through dysregulation of the extracellular matrix (ECM). CAFs are a heterogenous population derived from different cell types through activation and reprogramming. Current studies rely on uncharacterized heterogenous primary CAFs or normal fibroblasts that fail to recapitulate CAF-like tumor behavior. Here, we present that conditioned media from ovarian cancer lines leads to an increase in the activated state of fibroblasts demonstrated by functional assays and up-regulation of known CAF-related genes and ECM pathways. Phenotypic and functional characterization demonstrated that the conditioned CAFs expressed a CAF-like phenotype, strengthened proliferation, secretory, contractility, and ECM remodeling properties when compared to resting normal fibroblasts, consistent with an activated fibroblast status. Moreover, conditioned CAFs significantly enhanced drug resistance and tumor progression. Critically, the conditioned CAFs resemble a transcriptional signature with involvement of ECM remodeling. The present study provides mechanistic and functional insights about the activation and reprogramming of CAFs in the ovarian tumor microenvironment mediated by non-vesicular paracrine signaling. Moreover, it provides a translational based approach to reprogram normal fibroblasts from both uterine and ovarian origin into CAFs using tumor-derived conditioned media. Using these resources, further development of therapeutics that possess potentiality and specificity towards CAF/ECM-mediated chemoresistance in OC are further warranted.</p></div>","PeriodicalId":8754,"journal":{"name":"Biochimica et biophysica acta. Molecular cell research","volume":"1871 7","pages":"Article 119801"},"PeriodicalIF":4.6,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0167488924001447/pdfft?md5=f551f99dfef9248f1d39f3366e526b0d&pid=1-s2.0-S0167488924001447-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}