Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling

Autor: Bernadette Hritzo, Saeed Yadranji Aghdam, Nabarun Chakraborty, Maria Moroni, Alena Tsioplaya, Gregory P. Holmes-Hampton, Amandeep Kaur, Betre Legesse, Rasha Hammamieh, William Wilkins, George Dimitrov, Marjan Boerma, Aarti Gautam, Maohua Cao
Rok vydání: 2021
Předmět:
0301 basic medicine
Swine
lcsh:Chemistry
0302 clinical medicine
Fibrosis
Heart Rate
Hyperinsulinemia
Insulin-Like Growth Factor I
lcsh:QH301-705.5
Spectroscopy
Kidney
General Medicine
Göttingen minipig
Computer Science Applications
medicine.anatomical_structure
Insulin-like growth factor-1
Organ Specificity
030220 oncology & carcinogenesis
IGF-1
Collagen
Signal Transduction
medicine.medical_specialty
partial body irradiation
Catalysis
Article
Growth hormone deficiency
Inorganic Chemistry
03 medical and health sciences
Internal medicine
Diabetes mellitus
medicine
Animals
late effects
Physical and Theoretical Chemistry
Radiation Injuries
Molecular Biology
Blood Cells
Myocardium
Organic Chemistry
Body Weight
Dose-Response Relationship
Radiation
medicine.disease
Lipid Metabolism
Hematopoiesis
radiation
Disease Models
Animal
030104 developmental biology
MRNA Sequencing
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
Gene Expression Regulation
Metabolic syndrome
Biomarkers
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 6
International Journal of Molecular Sciences, Vol 22, Iss 3286, p 3286 (2021)
ISSN: 1422-0067
Popis: Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9–2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation
collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.
Databáze: OpenAIRE
Externí odkaz: