scholarly journals Mechanistic insights into immunomodulation by hepatic stellate cells in mice: A critical role of interferon-γ signaling

Hepatology ◽  
2009 ◽  
Vol 50 (6) ◽  
pp. 1981-1991 ◽  
Author(s):  
Horng-Ren Yang ◽  
Hong-Shuie Chou ◽  
Xiaodong Gu ◽  
Lianfu Wang ◽  
Kathleen E. Brown ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Critical Role ◽  
Stellate Cells ◽  
Interferon Γ

scholarly journals Remodeling of hepatic stellate cells orchestrated the stroma-derived oxaliplatin-resistance through CCN3 paracrine in hepatocellular carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xia Liao ◽  
Yang Bu ◽  
Fan Chang ◽  
Fengan Jia ◽  
Ge Song ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatic Stellate Cells ◽  
Critical Role ◽  
Stellate Cells ◽  
Clinical Samples ◽  
Pathway Activation ◽  
The Relationship

Abstract Background Hepatic stellate cells (HSCs) have a key role in fibrogenesis and in the filtrates of the hepatocellular carcinoma (HCC) stroma, in which they are remodeled and play a critical role in HCC progression. However, the precise role of HSCs trending, infiltration and paracrine in orchestrating the stroma-derived oxaliplatin-resistance in HCC is still vague. Methods The chemo-resistant models were established to explore the correlation between HSC cells and the condition of chemoresistance. The HCC clinical samples were collected to confirm this phenomenon. Then, the relationship between secretory CCN3 from oxaliplatin-resistant HCC and the infiltration of HSCs in associated HCC microenvironment was evaluated. Finally, the role and mechanism of HSCs remodeling in the orchestration of oxaliplatin-resistant HCC were explored. Results The increased infiltration of HSCs and collagen accumulation were found in the microenvironment of oxaliplatin-resistant HCC. The cDNA profiles of the oxaliplatin-resistant HCC was reanalyzed, and CCN3 was one of the significantly increased genes. In HCC clinical samples, the levels of CCN3 and α-SMA are positively correlated, and high expression of CCN3 and α-SMA are positively associated with malignant phenotype and poor prognosis. Then the enhanced abilities of migration and proliferation of HSCs, and elevation of the cytokines paracrine from HSCs relating to HCC malignancy were proved in vitro and in vivo, and which were related to CCN3-ERK signaling pathway activation. Conclusions HSCs remodeling are positively related to CCN3 paracrine in hepatocellular carcinoma, which orchestrated the stroma-derived resistance to chemotherapy in HCC.

scholarly journals Inhibition of SIRT2 suppresses hepatic fibrosis

2016 ◽  
Vol 310 (11) ◽  
pp. G1155-G1168 ◽  
Author(s):  
Maribel Arteaga ◽  
Na Shang ◽  
Xianzhong Ding ◽  
Sherri Yong ◽  
Scott J. Cotler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Histone Deacetylases ◽  
Critical Role ◽  
Stellate Cells ◽  
Novel Strategy ◽  
Underlying Mechanisms

Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

scholarly journals A critical role of TRAIL expressed on cotransplanted hepatic stellate cells in prevention of islet allograft rejection

Microsurgery ◽  
2009 ◽  
Vol 30 (4) ◽  
pp. 332-337 ◽  
Author(s):  
Horng-Ren Yang ◽  
Ching-Chuan Hsieh ◽  
Lianfu Wang ◽  
John J. Fung ◽  
Lina Lu ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Allograft Rejection ◽  
Critical Role ◽  
Stellate Cells ◽  
Islet Allograft

Fibrogenic actions of acetaldehyde are β-catenin dependent but Wingless independent: A critical role of nucleoredoxin and reactive oxygen species in human hepatic stellate cells

2013 ◽  
Vol 65 ◽  
pp. 1487-1496 ◽  
Author(s):  
Jaime Arellanes-Robledo ◽  
Karina Reyes-Gordillo ◽  
Ruchi Shah ◽  
José Alfredo Domínguez-Rosales ◽  
Zamira Helena Hernández-Nazara ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hepatic Stellate Cells ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Stellate Cells ◽  
Oxygen Species

Sa.117. Laboratory Immunology@A Critical Role of B7-H1 in Protection of Islet Allografts By Co-Transplanted Hepatic Stellate Cells

2006 ◽  
Vol 119 ◽  
pp. S146-S147
Author(s):  
Lina Lu ◽  
Cheng-Hsu Chen ◽  
Liang-Mou Kuo ◽  
Wenhan Wu ◽  
John Fung ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Critical Role ◽  
Stellate Cells ◽  
Islet Allografts

scholarly journals The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Yong Tang ◽  
Marie J. Desierto ◽  
Jichun Chen ◽  
Neal S. Young
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Transcription Factor ◽  
Transforming Growth Factor ◽  
Bone Marrow Failure ◽  
Critical Role ◽  
Interferon Γ ◽  
Interleukin 17 ◽  
Immune Mediated

Abstract The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet−/−). In comparison with normal C57BL6 (B6) control mice, T-bet−/− mice had normal cellular composition in lymphohematopoietic tissues, but T-bet−/− lymphocytes were functionally defective. Infusion of 5 × 106 T-bet−/− lymph node (LN) cells into sublethally irradiated, major histocompatibility complex–mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet−/− LN-cell dose to 10 to 23 × 106 per recipient led to only mild hematopoietic deficiency. Recipients of T-bet−/− LN cells had no expansion in T cells or interferon-γ–producing T cells but showed a significant increase in Lin−Sca1+CD117+CD34− BM cells. Plasma transforming growth factor-β and interleukin-17 concentrations were increased in T-bet−/− LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-γ resulted in hematopoietic suppression but did not cause T-bet−/− LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

scholarly journals Role of DDAH/ADMA pathway in TGF-β1-mediated activation of hepatic stellate cells

2017 ◽  
Author(s):  
Zhenguo Liu ◽  
Juan Wang ◽  
Wu Xing ◽  
Yingqiong Peng ◽  
Yan Huang ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Tgf Β1

A non-autonomous role of MKL1 in the activation of hepatic stellate cells

2019 ◽  
Vol 1862 (6) ◽  
pp. 609-618 ◽  
Author(s):  
Zilong Li ◽  
Ping Li ◽  
Yunjie Lu ◽  
Donglin Sun ◽  
Xiaoying Zhang ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells
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