Preclinical studies of a death receptor 5 fusion protein that ameliorates acute liver failure

Chen, Qian; Wang, Pu; Zhang, Qingmei; Xia, Meng; Zhang, Guizhong; Li, Junxin; Shen, Enyun; Chen, Youhai H.; Wan, Xiaochun

doi:10.1007/s00109-019-01813-w

Cited by 2 publications

(1 citation statement)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…sDR5-Fc fusion protein, by recombinant expression with human sDR5 and the Fc domain of human immunoglobulin G1, is more stable than sDR5 with a long half-life in vivo ( Song et al, 2000 ; Peng et al, 2022 ). In previous studies, sDR5-Fc can effectively blocked TRAIL-induced apoptosis, inflammation and had good therapeutic effect on ischemia and heart-reperfusion ( Wang et al, 2020 ), alleviate liver injury, inflammation, significantly reduce hepatocyte apoptosis and protect liver function ( Chen et al, 2019 ; Chen et al, 2020 ), as well as reduce inflammation induced by SARS-CoV-2 ( Peng et al, 2022 ). However, although many studies had focused on the possible therapeutic effects of TRAIL and its receptor DR5 in related diseases such as cancer and virus or inflammation-related disease, the role of TRAIL-DR5 pathway in ARS is unclear.…”

Section: Introductionmentioning

confidence: 99%

Blocking TRAIL-DR5 signaling pathway with soluble death receptor 5 fusion protein mitigates radiation-induced injury

et al. 2023

View full text Add to dashboard Cite

The increasing application of nuclear technology, the high fatality of acute radiation syndrome (ARS) and its complex mechanism make ARS a global difficulty that requires urgent attention. Here we reported that the death receptor 5 (DR5), as well as its ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were both significantly upregulated after irradiation in mice with 6 Gy γ-ray single radiation. And by intravenously administrated with soluble DR5 fusion protein (sDR5-Fc), the competitive antagonist of DR5, the excessive apoptosis in the radiation-sensitive tissues such as spleen and thymus were significantly inhibited and the radiation-induced damage of spleen and thymus were mitigated, while the expression of apoptosis-inhibiting proteins such as Bcl-2 was also significantly upregulated. The biochemical indicators such as serum ALP, AST, ALT, TBIL, K, and Cl levels that affected by radiation, were improved by sDR5-Fc administration. sDR5-Fc can also regulate the number of immune cells and reduce blood cell death. For in vitro studies, it had been found that sDR5-Fc effectively inhibited apoptosis of human small intestinal mucosal epithelial cells and IEC-6 cells using flow cytometry. Finally, survival studies showed that mice administrated with sDR5-Fc after 9 Gy γ-ray single whole body radiation effectively increased the 30-day survival and was in a significant dose-dependent manner. Overall, the findings revealed that DR5/TRAIL-mediated apoptosis pathway had played important roles in the injury of ARS mice, and DR5 probably be a potential target for ARS therapeutics. And the DR5 apoptosis antagonist, sDR5 fusion protein, probably is a promising anti-ARS drug candidate which deserves further investigation.

show abstract