dTMP-GH Fusion Protein Therapy Improves Survival after Radiation Injury Combined with Skin-Burn Trauma in Mice.

Abstract

Exposure to ionizing radiation combined with traumatic tissue injury is an important life-threatening condition found in the civilian populations after nuclear and radiological events. The significance feature of radiation combined injury (RCI) is the severe combined effect, which makes the injury more complicated. At present, there are limited measures available to treat RCI. Here we show that a chimeric protein dTMP-GH, fusing human growth hormone (hGH) with a tandem dimer of thrombopoietin mimetic peptide (dTMP), could be an effective therapy agent for RCI in a mice model. In this study, using a RCI mouse model exposed to 60Co γ-ray photons (6.0 Gy, 0.3 Gy/min) followed by a 20% total-body-surface-area burns (henceforth called: RB-CI) was established. Administration of dTMP-GH (200 ug/kg) for 10 consecutive days beginning at 24 h after injury improved survival rate during a 30-day observation period compared with the control vehicle group. dTMP-GH treatment also showed enhanced bone marrow hematopoiesis recovery determined by peripheral blood analysis and bone marrow histopathology. Meanwhile, dTMP-GH treatment accelerated skin wound closure and mitigated ileum injury in the RCI model. These results suggest that dTMP-GH may prove to be an effective therapeutic drug for RCI.

• Authors: Shuang Long, Guojian Wang, Mingqiang Shen, Na Zhao, Huimin Wan, Yang Xu, Song Wang, Cheng Wang, Jining Gao, Yuhui Hao, Aiping Wang, Rong Li, Xinze Ran, Yongping Su, Junping Wang, Tao Wang
• Journal: Radiation research (Radiat Res) Vol. 191 Issue 4 Pg. 360-368 (04 2019) ISSN: 1938-5404 [Electronic] United States
• PMID: 30759046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptides
• Recombinant Fusion Proteins
• thrombopoietin mimetic peptide
• Human Growth Hormone

Topics

• Animals
• Burns (complications)
• Human Growth Hormone (genetics, therapeutic use)
• Humans
• Ileum (drug effects, radiation effects)
• Male
• Mice
• Peptides (chemistry, genetics)
• Protein Multimerization
• Radiation Injuries, Experimental (complications, drug therapy, pathology, physiopathology)
• Recombinant Fusion Proteins (genetics, therapeutic use)
• Skin (pathology)
• Survival Analysis
• Wound Healing (drug effects, radiation effects)