NDLI: Ghrelin, a novel therapy, corrects cytokine and NF-κB-AKT-MAPK network and mitigates intestinal injury induced by combined radiation and skin-wound trauma

Content Provider	Springer Nature : BioMed Central
Author	Kiang, Juliann G. Smith, Joan T. Cannon, Georgetta Anderson, Marsha N. Ho, Connie Zhai, Min Cui, Wanchang Xiao, Mang
Abstract	Background Compared to radiation injury alone (RI), radiation injury combined wound (CI) further enhances acute radiation syndrome and subsequently mortality. We previously reported that therapy with Ghrelin, the 28-amino-acid-peptide secreted from the stomach, significantly increased 30-day survival and mitigated hematopoietic death by enhancing and sustaining granulocyte-colony stimulating factor (G-CSF) and keratinocyte chemoattractant (KC) in the blood and bone marrow; increasing circulating white blood cell depletion; inhibiting splenocytopenia; and accelerating skin-wound healing on day 30 after CI. Herein, we aimed to study the efficacy of Ghrelin on intestinal injury at early time points after CI. Methods B6D2F1/J female mice were exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral), followed by 15% total-body-surface-area skin wounds. Several endpoints were measured: at 4–5 h and on days 1, 3, 7, and 15. Results Ghrelin therapy mitigated CI-induced increases in IL-1β, IL-6, IL-17A, IL-18, KC, and TNF-α in serum but sustained G-CSF, KC and MIP-1α increases in ileum. Histological analysis of ileum on day 15 showed that Ghrelin treatment mitigated ileum injury by increasing villus height, crypt depth and counts, as well as decreasing villus width and mucosal injury score. Ghrelin therapy increased AKT activation and ERK activation; suppressed JNK activation and caspase-3 activation in ileum; and reduced NF-κB, iNOS, BAX and Bcl-2 in ileum. This therapy recovered the tight junction protein and mitigated bacterial translocation and lipopolysaccharides levels. The results suggest that the capacity of Ghrelin therapy to reduce CI-induced ileum injury is mediated by a balanced NF-κB-AKT-MAPK network that leads to homeostasis of pro-inflammatory and anti-inflammatory cytokines. Conclusions Our novel results are the first to suggest that Ghrelin therapy effectively decreases intestinal injury after CI.
Related Links	https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-020-00425-z.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	20453701
DOI	10.1186/s13578-020-00425-z
Journal	Cell & Bioscience
Issue Number	1
Volume Number	10
Language	English
Publisher	BioMed Central
Publisher Date	2020-05-12
Access Restriction	Open
Subject Keyword	Cell Biology Microbiology Stem Cells Neurobiology Proteomics Ionizing radiation Skin wound Ghrelin GI NF-κB AKT ERK JNK MAPK iNOS BAX Bcl-2 Caspase Tight junction Apoptosis Bacteria
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	7/2023

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