دورية أكاديمية
Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis
| العنوان: | Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis |
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| المؤلفون: | Bobowski-Gerard, Marie, Boulet, Clémence, Zummo, Francesco, Dubois-Chevalier, Julie, Gheeraert, Céline, Bou Saleh, Mohamed, Strub, Jean-Marc, Farce, Amaury, Ploton, Maheul, Guille, Loïc, Vandel, Jimmy, Bongiovanni, Antonino, Very, Ninon, Woitrain, Eloïse, Deprince, Audrey, Lalloyer, Fanny, Bauge, Eric, Ferri, Lise, Ntandja-Wandji, Line-Carolle, Cotte, Alexia, Grangette, Corinne, Vallez, Emmanuelle, Cianférani, Sarah, Raverdy, Violeta, Caiazzo, Robert, Gnemmi, Viviane, Leteurtre, Emmanuelle, Pourcet, Benoit, Paumelle, Réjane, Ravnskjaer, Kim, Lassailly, Guillaume, Haas, Joel, Mathurin, Philippe, Pattou, François, Dubuquoy, Laurent, Staels, Bart, Lefebvre, Philippe, Eeckhoute, Jérôme |
| المساهمون: | Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Institut de Pathologie CHU Lille, Pôle de Biologie Pathologie Génétique CHU Lille, Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Réseau International des Instituts Pasteur (RIIP), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Lille (CHU de Lille), ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016), ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-21-CE14-0032,HSCreg,Identification et caractérisation d'un nouveau facteur de transcription controlant l'activation des cellules stellaires et la fibrose hépatique(2021), ANR-20-CE14-0034,DeCodeNASH,L'activation métabolique des cellules dendritiques dans la steatopathie métabolique(2020), ANR-21-CE17-0016,MEdicAL,Cibler les MEcanismes cellulaires du défaut de régénération pour le développement d'une médecine de précision pour l'hépatite ALcoolique.(2021) |
| المصدر: | ISSN: 2041-1723. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2022 |
| المجموعة: | LillOA (HAL Lille Open Archive, Université de Lille) |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Abstract Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor. Using liver fibrosis as a model for in-depth investigations, we first show that BNC2 expression is induced in both mouse and human fibrotic livers from different etiologies and decreases upon human liver fibrosis regression. Importantly, we found that BNC2 transcriptional induction is a specific feature of myofibroblastic activation in fibrotic tissues. Mechanistically, BNC2 expression and activities allow to integrate pro-fibrotic stimuli, including TGFβ and Hippo/YAP1 signaling, towards induction of matrisome genes such as those encoding type I collagen. As a consequence, Bnc2 deficiency blunts collagen deposition in livers of mice fed a fibrogenic diet. Additionally, our work establishes BNC2 as potentially druggable since we identified the thalidomide derivative CC-885 as a BNC2 inhibitor. Altogether, we propose that BNC2 is a transcription factor involved in canonical pathways driving myofibroblastic activation in fibrosis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03774786; https://hal.science/hal-03774786Test; https://hal.science/hal-03774786/documentTest; https://hal.science/hal-03774786/file/s41467-022-33063-9.pdfTest |
| DOI: | 10.1038/s41467-022-33063-9 |
| الإتاحة: | https://doi.org/10.1038/s41467-022-33063-9Test https://hal.science/hal-03774786Test https://hal.science/hal-03774786/documentTest https://hal.science/hal-03774786/file/s41467-022-33063-9.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.615922B1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-022-33063-9 |
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