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

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http://hdl.handle.net/10138/332435

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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-w

Title: Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment
Author: 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
Contributor organization: Institute for Molecular Medicine Finland
Helsinki Institute of Life Science HiLIFE
University of Helsinki
Date: 2021-04-29
Language: eng
Number of pages: 13
Belongs to series: Cell Death and Disease
ISSN: 2041-4889
DOI: https://doi.org/10.1038/s41419-021-03704-w
URI: http://hdl.handle.net/10138/332435
Abstract: 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.
Subject: 1182 Biochemistry, cell and molecular biology
NF-KAPPA-B
HEPATIC RECRUITMENT
IMMUNE REGULATION
GILZ EXPRESSION
T-LYMPHOCYTES
TISSUE-DAMAGE
MURINE MODEL
CELLS
PROMOTES
INFLAMMATION
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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