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 ◽  
...  
BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xia Liao ◽  
Yang Bu ◽  
Fan Chang ◽  
Fengan Jia ◽  
Ge Song ◽  
...  

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.


2016 ◽  
Vol 310 (11) ◽  
pp. G1155-G1168 ◽  
Author(s):  
Maribel Arteaga ◽  
Na Shang ◽  
Xianzhong Ding ◽  
Sherri Yong ◽  
Scott J. Cotler ◽  
...  

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.


2013 ◽  
Vol 65 ◽  
pp. 1487-1496 ◽  
Author(s):  
Jaime Arellanes-Robledo ◽  
Karina Reyes-Gordillo ◽  
Ruchi Shah ◽  
José Alfredo Domínguez-Rosales ◽  
Zamira Helena Hernández-Nazara ◽  
...  

Hepatology ◽  
2009 ◽  
Vol 50 (6) ◽  
pp. 1981-1991 ◽  
Author(s):  
Horng-Ren Yang ◽  
Hong-Shuie Chou ◽  
Xiaodong Gu ◽  
Lianfu Wang ◽  
Kathleen E. Brown ◽  
...  

2006 ◽  
Vol 119 ◽  
pp. S146-S147
Author(s):  
Lina Lu ◽  
Cheng-Hsu Chen ◽  
Liang-Mou Kuo ◽  
Wenhan Wu ◽  
John Fung ◽  
...  

Author(s):  
Zhenguo Liu ◽  
Juan Wang ◽  
Wu Xing ◽  
Yingqiong Peng ◽  
Yan Huang ◽  
...  

Author(s):  
Zilong Li ◽  
Ping Li ◽  
Yunjie Lu ◽  
Donglin Sun ◽  
Xiaoying Zhang ◽  
...  

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