Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment
| العنوان: | Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment |
|---|---|
| المؤلفون: | Zenobio Viana de Barros, Timofei S. Zatsepin, Carlo Riccardi, Oxana Bereshchenko, Chiara Fiorucci, Graziella Migliorati, Stefano Pagano, Michele Biagioli, Tommaso Mello, Philipp Sergeev, Tatiana Prikazchikova, Musetta Paglialunga, Sara Flamini, Andrea Gagliardi, Stefano Bruscoli |
| المساهمون: | Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, University of Helsinki |
| المصدر: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 5, Pp 1-13 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | GILZ EXPRESSION, Liver Cirrhosis, Male, Cancer Research, Leucine zipper, CCR2, PROMOTES, Immunology, NF-KAPPA-B, Inflammation, CCL2, Article, TISSUE-DAMAGE, 03 medical and health sciences, Cellular and Molecular Neuroscience, Mice, 0302 clinical medicine, T-LYMPHOCYTES, INFLAMMATION, Leukocytes, Medicine, Gene silencing, Animals, Humans, Receptor, Chemokine CCL2, 030304 developmental biology, Mice, Knockout, Transcription Factors, 0303 health sciences, QH573-671, business.industry, HEPATIC RECRUITMENT, MURINE MODEL, Cell Biology, Chronic inflammation, Hepatic stellate cell activation, Experimental models of disease, IMMUNE REGULATION, 030220 oncology & carcinogenesis, Knockout mouse, CELLS, Cancer research, 1182 Biochemistry, cell and molecular biology, medicine.symptom, business, Cytology |
| 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. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07ad2f5a5451cef18f7bce62b6ab8599Test http://hdl.handle.net/2158/1256619Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....07ad2f5a5451cef18f7bce62b6ab8599 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |