Dataset Information

Hepatic stellate cells express thymosin Beta 4 in chronically damaged liver.

ABSTRACT: Although the various biological roles of thymosin ?4 (T?4) have been studied widely, the effect of T?4 and T?4-expressing cells in the liver remains unclear. Therefore, we investigated the expression and function of T?4 in chronically damaged livers. CCl4 was injected into male mice to induce a model of chronic liver disease. Mice were sacrificed at 6 and 10 weeks after CCl4 treatment, and the livers were collected for biochemical analysis. The activated LX-2, human hepatic stellate cell (HSC) line, were transfected with T?4-specific siRNA and activation markers of HSCs were examined. Compared to HepG2, higher expression of T?4 in RNA and protein levels was detected in the activated LX-2. In addition, T?4 was up-regulated in human liver with advanced liver fibrosis. The expression of T?4 increased during mouse HSC activation. T?4 was also up-regulated and T?4-positive cells were co-localized with ?-smooth muscle actin (?-SMA) in the livers of CCl4-treated mice, whereas such cells were rarely detected in the livers of corn-oil treated mice. The suppression of T?4 in LX-2 cells by siRNA induced the down-regulation of HSC activation-related genes, tgf-?, ?-sma, collagen, and vimentin, and up-regulation of HSC inactivation markers, ppar-? and gfap. Immunofluorescent staining detected rare co-expressing cells with T?4 and ?-SMA in T?4 siRNA-transfected cells. In addition, cytoplasmic lipid droplets were observed in T?4 siRNA-treated cells. These results demonstrate that activated HSCs expressed T?4 in chronically damaged livers, and this endogenous expression of T?4 influenced HSC activation, indicating that T?4 might contribute to liver fibrosis by regulating HSC activation.

SUBMITTER: Kim J

PROVIDER: S-EPMC4380456 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hepatic stellate cells express thymosin Beta 4 in chronically damaged liver.

Kim Jieun J Wang Sihyung S Hyun Jeongeun J Choi Steve S SS Cha Heejae H Ock Meesun M Jung Youngmi Y

PloS one 20150331 3

Although the various biological roles of thymosin β4 (Tβ4) have been studied widely, the effect of Tβ4 and Tβ4-expressing cells in the liver remains unclear. Therefore, we investigated the expression and function of Tβ4 in chronically damaged livers. CCl4 was injected into male mice to induce a model of chronic liver disease. Mice were sacrificed at 6 and 10 weeks after CCl4 treatment, and the livers were collected for biochemical analysis. The activated LX-2, human hepatic stellate cell (HSC) l ...[more]

PMID: 25826335

Similar Datasets

Project description:BackgroundHepatic fibrosis is caused by chronic liver injury and may progress toward liver cirrhosis, and even hepatocellular carcinoma. However, current treatment is not satisfactory. Therefore, there is a mandate to find novel therapeutic targets to improve therapy, and biomarkers to monitor therapeutic response.MethodsLiver fibrosis was induced by carbon tetrachloride (CCl4) or thioacetamide (TAA) in wild type (WT) or CTHRC1-/- mice, followed by immunofluorescence and immunohistochemical analyses. CTHRC1 monoclonal antibody (mAb) was used to abrogate the effect of CTHRC1 in vitro and in vivo.ResultsHere, we reported that collagen triple helix repeat containing 1 (CTHRC1), a secreted protein derived from hepatic stellate cells (HSCs), was significantly up-regulated in fibrotic liver tissues. CTHRC1 promoted HSCs transformation from a quiescent to an activated state, and enhanced migratory or contractile capacities of HSCs by activating TGF-β signaling. Meanwhile, CTHRC1 competitively bound to Wnt noncononical receptor and promoted the contractility but not activation of HSCs. CCl4 or TAA-induced liver fibrosis was attenuated in CTHRC-/- mice compared with littermate control, while a monoclonal antibody of CTHRC1 suppressed liver fibrosis in WT mice treated with CCl4 or TAA.InterpretationWe demonstrated that CTHRC1 is a new regulator of liver fibrosis by modulating TGF-β signaling. Targeting CTHRC1 could be a promising therapeutic approach, which can suppress TGF-β signaling and avoid the side effects caused by directly targeting TGF-β. CTHRC1 could also be a potential biomarker for monitoring response to anti-fibrotic therapy. FUND: This study was supported by the National Natural Science Foundation of China (ID 81672358, 81871923, 81872242, 81802890), the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (ID 20181708), the Natural Science Foundation of Shanghai (ID 17ZR1428300, 18ZR1436900), and Shanghai Municipal Health Bureau (ID 2018BR32). The funders did not play a role in manuscript design, data collection, data analysis, interpretation nor writing of the manuscript.

Dataset Information

Hepatic stellate cells express thymosin Beta 4 in chronically damaged liver.

Publications

Hepatic stellate cells express thymosin Beta 4 in chronically damaged liver.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets