دورية أكاديمية

Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment

التفاصيل البيبلوغرافية
العنوان: Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment
المؤلفون: Flamini, Sara, Sergeev, Philipp, Viana de Barros, Zenobio, Mello, Tommaso, Biagioli, Michele, Paglialunga, Musetta, Fiorucci, Chiara, Prikazchikova, Tatiana, Pagano, Stefano, Gagliardi, Andrea, Riccardi, Carlo, Zatsepin, Timofei, Migliorati, Graziella, Bereshchenko, Oxana, Bruscoli, Stefano
المساهمون: Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, University of Helsinki
بيانات النشر: Nature Publishing Group
سنة النشر: 2021
المجموعة: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
مصطلحات موضوعية: 1182 Biochemistry, cell and molecular biology, NF-KAPPA-B, HEPATIC RECRUITMENT, IMMUNE REGULATION, GILZ EXPRESSION, T-LYMPHOCYTES, TISSUE-DAMAGE, MURINE MODEL, CELLS, PROMOTES, INFLAMMATION
الوصف: Liver fibrosis (LF) is a dangerous clinical condition with no available treatment. Inflammation plays a critical role in LF progression. Glucocorticoid-induced leucine zipper (GILZ, encoded in mice by the Tsc22d3 gene) mimics many of the anti-inflammatory effects of glucocorticoids, but its role in LF has not been directly addressed. Here, we found that GILZ deficiency in mice was associated with elevated CCL2 production and pro-inflammatory leukocyte infiltration at the early LF stage, resulting in enhanced LF development. RNA interference-mediated in vivo silencing of the CCL2 receptor CCR2 abolished the increased leukocyte recruitment and the associated hepatic stellate cell activation in the livers of GILZ knockout mice. To highlight the clinical relevance of these findings, we found that TSC22D3 mRNA expression was significantly downregulated and was inversely correlated with that of CCL2 in the liver samples of patients with LF. Altogether, these data demonstrate a protective role of GILZ in LF and uncover the mechanism, which can be targeted therapeutically. Therefore, modulating GILZ expression and its downstream targets represents a novel avenue for pharmacological intervention for treating LF and possibly other liver inflammatory disorders. ; Peer reviewed
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: Flamini , S , Sergeev , P , Viana de Barros , Z , Mello , T , Biagioli , M , Paglialunga , M , Fiorucci , C , Prikazchikova , T , Pagano , S , Gagliardi , A , Riccardi , C , Zatsepin , T , Migliorati , G , Bereshchenko , O & Bruscoli , S 2021 , ' Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment ' , Cell Death and Disease , vol. 12 , no. 5 , 421 . https://doi.org/10.1038/s41419-021-03704-wTest; RIS: urn:30F7BE897080E12BE239E79352AD92E2; RIS: Flamini2021; ORCID: /0000-0002-0234-1568/work/97058478; 70609ce7-3519-48e8-b818-b7ed848b8a5d; http://hdl.handle.net/10138/332435Test; 000656149600001
الإتاحة: http://hdl.handle.net/10138/332435Test
حقوق: cc_by ; openAccess ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.5D9B62C8
قاعدة البيانات: BASE