Advanced Glycation End Products Induce Proliferation and Migration of Human Aortic Smooth Muscle Cells through PI3K/AKT Pathway

Yuan, Gang; Si, Guangyan; Hou, Qingchun; Li, Zhaonan; Xu, Kaiqiang; Wang, Yuping; Wang, Weiming; Xu, Xiongfei; Zhang, Lei; Sun, Xiaolei; He, Hongwu; Zeng, Hong; Liu, Yong

doi:10.1155/2020/8607418

Cited by 13 publications

(8 citation statements)

References 29 publications

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“…The interaction of advanced glycation end products (AGEs) and receptor of advanced glycation end product (RAGE) ( Figure 3 ) in the vascular system of diabetic patients activates downstream PI3K/AKT pathways, thereby promoting human aorta VSMC proliferation and migration. Consequently, inhibition of the PI3K/AKT pathway may become a new strategy for the treatment of diabetic atherosclerosis ( Yuan et al, 2020 ). Rosiglitazone ( Figure 3 ) has been reported to inhibit insulin-stimulated VSMC proliferation by inhibiting the PI3K/Akt/mTOR/P70S6K cascades ( Park et al, 2008 ).…”

Section: Pi3k-targeted Therapy In Atherosclerosismentioning

confidence: 99%

Role of PI3K in the Progression and Regression of Atherosclerosis

et al. 2021

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Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

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Section: Pi3k-targeted Therapy In Atherosclerosismentioning

confidence: 99%

Role of PI3K in the Progression and Regression of Atherosclerosis

et al. 2021

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“…As demonstrated in Figure 1A , the administration of AGEs induced Ca 2+ deposition (black deposits) in our cellular model in a dose-dependent manner, within the range of 25 mg/L to 100 mg/L compared to no AGEs treatment. The concentrations used were based on the preliminary experiments ( Yuan et al, 2020 ) that stimulate calcification in HVSMC in a dose-dependent manner in vitro ( Kay et al, 2016 ). Sayo Koike's study produced the same results ( Koike et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

AGEs-Induced Calcification and Apoptosis in Human Vascular Smooth Muscle Cells Is Reversed by Inhibition of Autophagy

Law

et al. 2021

Front. Pharmacol.

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Vascular calcification (VC) in macrovascular and peripheral blood vessels is one of the main factors leading to diabetes mellitus (DM) and death. Apart from the induction of vascular calcification, advanced glycation end products (AGEs) have also been reported to modulate autophagy and apoptosis in DM. Autophagy plays a role in maintaining the stabilization of the external and internal microenvironment. This process is vital for regulating arteriosclerosis. However, the internal mechanisms of this pathogenic process are still unclear. Besides, the relationship among autophagy, apoptosis, and calcification in HASMCs upon AGEs exposure has not been reported in detail. In this study, we established a calcification model of SMC through the intervention of AGEs. It was found that the calcification was upregulated in AGEs treated HASMCs when autophagy and apoptosis were activated. In the country, AGEs-activated calcification and apoptosis were suppressed in Atg7 knockout cells or pretreated with wortmannin (WM), an autophagy inhibitor. These results provide new insights to conduct further investigations on the potential clinical applications for autophagy inhibitors in the treatment of diabetes-related vascular calcification.

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“…Supplementary to these previous findings, the current study further showed that AGEs upregulated the expression of K17 and resulted in the nuclear export and degradation of p27 KIP1 , leading to progressed cell cycle and ultimately the proliferation of keratinocytes. Multiple studies have demonstrated the pro-proliferative effects of AGEs on different types of cells like mesangial cells and aortic smooth muscle cells [25][26][27]. However, some other studies have claimed the inhibitory effects of AGEs on cell proliferation or cell cycle progression in ovarian granulosa cells and intestinal epithelial cells [58,59].…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis

Kang,

Chen,

Wang

et al. 2023

J Innate Immun

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Psoriasis is a common inflammatory skin disease, in which epidermal keratinocytes play a vital role in its pathogenesis by acting both as the responder and as the accelerator to the cutaneous psoriatic immune response. Advanced glycation end products (AGEs) are a class of proinflammatory metabolites that are commonly accumulating in cardiometabolic disorders. Recent studies have also observed the increased level of AGEs in the serum and skin of psoriasis patients, but the role of AGEs in psoriatic inflammation has not been well investigated. In the present study, we initially detected abnormal accumulation of AGEs in epidermal keratinocytes of psoriatic lesions collected from psoriasis patients. Furthermore, AGEs promoted the proliferation of keratinocytes via upregulated Keratin 17 (K17)-mediated p27<sup>KIP1</sup> inhibition followed by accelerated cell cycle progression. More importantly, AGEs facilitated the production of interleukin-36 alpha (IL-36α) in keratinocytes, which could enhance T helper 17 (Th17) immune response. In addition, the induction of both K17 and IL-36α by AGEs in keratinocytes was dependent on the activation of signal transducer and activator of transcription 1/3 (STAT1/3) signaling pathways. At last, the effects of AGEs on keratinocytes were mediated by the receptor for AGEs (RAGE). Taken together, these findings support that AGEs potentiate the innate immune function of keratinocytes, which contributes to the formation of psoriatic inflammation. Our study implicates AGEs as a potential pathogenic link between psoriasis and cardiometabolic comorbidities.

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Advanced Glycation End Products Induce Proliferation and Migration of Human Aortic Smooth Muscle Cells through PI3K/AKT Pathway

Cited by 13 publications

References 29 publications

Role of PI3K in the Progression and Regression of Atherosclerosis

Role of PI3K in the Progression and Regression of Atherosclerosis

AGEs-Induced Calcification and Apoptosis in Human Vascular Smooth Muscle Cells Is Reversed by Inhibition of Autophagy

Advanced Glycation End Products-Induced Activation of Keratinocytes: A Mechanism Underlying Cutaneous Immune Response in Psoriasis

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