The involvement of ACO3 protein in diabetic retinopathy through the PI3k/Akt signaling pathway

Abstract

Background. Diabetic retinopathy (DR) is one of the most common complications of diabetic microvascular disease and its pathogenesis is complicated. The PI3k/Akt signaling pathway plays an important role in the angiogenesis of DR. Objectives.To explore the molecular mechanisms of the ACO3 protein and related proteins in DR, in order to provide a scientific theoretical basis for the clinical treatment of this disease. Materials and methods.A DR rat model was used in this study. One group (anti-ACO3 group, n = 10) was injected with protein ACO3 antagonist; the 2 nd study group (the DR group, n = 10) was injected with the same amount of normal saline; the control group (n = 10) did not undergo any procedures. We used hematoxylin and eosin (H&E) staining to observe the pathological features of the eye tissues. Immunohistochemistry was used to analyze the expression of ACO3 and AKT. Western blot was used to analyze the expression of ANGPT1, ANGPT4 and KDR; reverse transcription polymerase chain reaction (RT-PCR) was used to assess the mRNA expression of AKT, ACO3 and SMOX in the eye tissues of the rats.Results. In the anti-ACO3 group, the results of H&E staining showed that there was a decrease in retinal edema and no obvious abnormality in the blood vessels. The immunohistochemistry analysis of proteins proved that ACO3 and AKT were strongly expressed in the DR group. The western blot analysis of ANGPT1, ANGPT4 and KDR expression showed that in the DR group, the expression of all 3 proteins was higher than in the anti-ACO3 group, and much higher than in the control group. Conclusions.The mRNA expression of AKT, ACO3 and SMOX was strong in the DR group, but decreased in the anti-ACO3 group.

Identification of Potential Molecular Targets and Active Ingredients of Mingmu Dihuang Pill for the Treatment of Diabetic Retinopathy Based on Network Pharmacology

“…PI3K/AKT signaling is a major pathway in insulin, and aberrant PI3K/AKT signaling is a common pathogenesis of diabetes [ 42 ]. Previous studies have demonstrated that PI3K/AKT signaling plays a critical role in the neovascularization of diabetic retinopathy, and upon activation, PI3K/AKT signaling may extend the survival period of endothelial cells and synergize with VEGF to jointly mediate cell survival and migration, which finally triggers neovascularization [ 43 , 44 ]. In addition, PI3K signaling may be activated by hypoglycemia and hypoxia under a diabetic condition, and activation of AKT may induce vascular dilation, remodeling, and vascularization [ 45 ].…”

“…PI3K/ AKT signaling is a major pathway in insulin, and aberrant PI3K/AKT signaling is a common pathogenesis of diabetes [42]. Previous studies have demonstrated that PI3K/AKT [43,44]. In addition, PI3K signaling may be activated by hypoglycemia and hypoxia under a diabetic condition, and activation of AKT may induce vascular dilation, remodeling, and vascularization [45].…”

RAGE plays key role in diabetic retinopathy: a review

“…PI3K/AKT signaling plays a key role in neovascularization in DR. Activation of PI3K/AKT signaling by AGEs combined with RAGE may prolong endothelial cell survival, and cooperate with VEGF to promote retinal endothelial cell proliferation and migration, ultimately promoting neovascularization [ 30 , 31 ]. Activated AKT can mediate a variety of downstream target proteins, such as cell growth and proliferation through phosphorylation of mTOR, and apoptosis through inhibition of adverse expression [ 32 , 33 ].…”