Ionizing radiation modulates vascular endothelial growth factor expression through STAT3 signaling pathway in rat neonatal primary astrocyte cultures

Abstract

Background and Purpose: Radiation-induced brain injury (RBI) usually occurs six months to three years after irradiation, often shows cognitive dysfunction, epilepsy, and other neurological dysfunction. In severe cases, it can cause a wide range of cerebral edema, even herniation. It seriously threatens the survival of patients and their quality of life, and it becomes a key factor in limiting the radiation dose and lowering the therapeutic efficacy in recent years. Therefore, studying the pathogenesis of RBI and exploring new therapeutic targets are of great significance.Methods: In our study, we observed the activation and secretory function in astrocytes as well as the intracellular signal transducer and activator of transcription 3 (STAT3) signal transduction pathway activation status after exposing different doses of X-ray irradiation by using MTT, Immunocytologic analysis, and Western blot analysis. Further, we used the same way to explore the role of vascular endothelial growth factor (VEGF) in signal transduction pathways playing in the activation of astrocytes after irradiating through the use of specificInhivascular endothelial growth factorbitors of STAT3.Results: Ast can be directly activated, reactive hyperplasia and hypertrophy, the expression of the activation marker glial fibrillary acidic protein is increased, and the expression of vascular endothelial growth factor (VEGF) in the cells is increased, which may lead to RBI. After the addition of STAT3 pathway inhibitor, most of the Ast radiation activation was suppressed, and the expression of high-level expression of VEGF decreased after irradiation. Conclusion:Our findings demonstrated that X-ray irradiation directly induced the activation of astrocytes in a persistent manner and X-ray irradiation activated STAT3 signaling pathway. As the same time, we found that X-ray irradiation induced the

Effect of Low-Dose Gamma Radiation and Lipoic Acid on High- Radiation-Dose Induced Rat Brain Injuries

“… 37 Knowing that NF-κB upregulates pro-inflammatory cytokines production, including that of IL-1β and TNF-α, which in turn increases BBB permeability and evolves demyelination and edema. 38 Previously, it was reported that TNF-α played a critical role in radiation-induced vascular damage, BBB disruption and astrogliosis, where the binding of TNF-α to its receptors on the endothelial cell surface activates NF-κB, which in turn upregulates the synthesis of intercellular adhesion molecule-1 causing increases leukocyte-endothelial cell interactions. Consequently, it increases infiltration of immune and inflammatory cells through the damaged BBB.…”

“…It was observed a positive correlation between the VEGF expression and the brain injury in mice exposed to 20 Gy whole-brain irradiation. 2 Besides, in vitro study has demonstrated that VEGF expression in astrocytes increased significantly in a dose-dependent manner (Zhou et al 2020). 39 However, VEGF inhibition may have a potential for treatment of brain injury in irradiated and ischemic experimental animals.…”

“…2 Besides, in vitro study has demonstrated that VEGF expression in astrocytes increased significantly in a dose-dependent manner (Zhou et al 2020). 39 However, VEGF inhibition may have a potential for treatment of brain injury in irradiated and ischemic experimental animals. 40,41 Moreover, it was suggested that oxidative stress has an essential role in Aβ peptides generation and accumulation in the brain tissues.…”

Role of JAK/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms

“…Our group described that JAK2 is overexpressed in a BLM-induced fibrosis rat [20,21] IL-13 → JAK1/TYK2 → STAT6 AECs from BLM-induced fibrosis mouse model [20,21] IL-6 → STAT3 IPF fibroblasts, normal lung fibroblasts and BLM-induced mouse model [22][23][24] IL-11 → STAT3 BLM-induced fibrosis mouse model, human lung fibroblasts [25][26][27] IL-31 → STAT1 Mouse pulmonary fibrosis [28] TGF-β1 → STAT3 Human fibroblasts, AECs, SS mouse model [29,30] TGF-β1 → JAK2 → STAT3 IPF AECs and fibroblasts, SS [31,32] EGF → STAT3 IPF, COP, NSIP [33,34] PDGF → STAT1 ILDs alveolar macrophages, IPF BALF [35][36][37] FGF → STAT1/STAT3/STAT5 Progressive fibrosing ILD [38,39] VEGF → STAT3 IPF, Idiopathic interstitial pneumonia [40,41] Abbreviations: alveolar epithelial cells (AECs), bleomycin (BLM), systemic sclerosis (SS), idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), idiopathic nonspecific interstitial pneumonia (NSIP), bronchoalveolar lavage fluid (BALF).…”

“…Recent evidence shows that VEGF constitutes an exhaled biomarker in IPF, with significant correlations with the clinical manifestations [55], and patients with idiopathic interstitial pneumonia have higher VEGF levels in plasma [56]. VEGF is associated with STAT3 in primary astrocytes when ionizing radiation-induced overexpression of VEGF leads to STAT3 activation [40]. Moreover, STAT3 has a binding site on the VEGF promoter and can regulate VEGF expression [41].…”