High Glucose Stimulates Expression of MFHAS1 to Mitigate Inflammation via Akt/HO-1 Pathway in Human Umbilical Vein Endot
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ORIGINAL ARTICLE
High Glucose Stimulates Expression of MFHAS1 to Mitigate Inflammation via Akt/HO-1 Pathway in Human Umbilical Vein Endothelial Cells Hui-hui Wang,1 Peng-fei Sun,1 Wan-kun Chen,1 Jing Zhong,1 Qi-qing Shi,2 Mei-lin Weng,1 Duan Ma,3,4 and Chang-hong Miao1,4
Hyperglycemia is a highly dangerous factor to various diseases, even resulting in death of people. Inflammation plays a key role in this process. The aim of this study was to explore the role of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) in highglucose induced inflammation. Our research showed that high glucose stimulated the expression of MFHAS1, and overexpression of MFHAS1 can attenuate high-glucose induced inflammation in endothelial cells by decreasing the secretion of cytokines interleukin-1β (IL-1β), interleukin-1α (IL-1α), adhesion molecule intercellular adhesion molecule-1 (ICAM), interleukin-6 (IL-6), interleukin-8 (IL-8), and chemokine ligand 1 (CXCL-1). Furthermore, we found that MFHAS1 promoted the phosphorylation of Akt and the expression of heme oxygenase-1 (HO-1). Our results indicated that MFHAS1 deadened highglucose induced inflammation by activating AKT/HO-1 pathway, suggesting that MFHAS1 may act as a new therapeutic target of diabetes mellitus.
Abstract—
KEY WORDS: high glucose; inflammation; MFHAS1; AKT; HO-1.
Hui-hui Wang and Peng-fei Sun contributed equally to this work.
INTRODUCTION
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-017-0696-0) contains supplementary material, which is available to authorized users.
Diabetes mellitus is one of the leading causes of morbidity and mortality in afflicted individuals. The International Diabetes Federation data have shown that there are more than 415 million people with diabetes mellitus worldwide, and it could rise to over 642 million or more by 2040 [1]. Hyperglycemia is the most prominent sign that characterizes diabetes [2]. There is a fair amount of evidence confirming that inflammation plays a key role in the pathogenesis of diabetes mellitus [3–5], and targeting the inflammation and its signaling pathways may be effective to manage diabetes mellitus and its associated complications including nephropathy, ischemic heart disease, peripheral vascular disease, and cerebrovascular disease [6]. However, the underlying mechanisms are poorly understood.
1
Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China 2 Children’s Hospital of Fudan University, Shanghai, 201102, China 3 Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative Innovation Center of Genetics and Development, Institute of Biomedical Sciences, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China 4 To whom correspondence should be addressed to Duan Ma at Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Collaborative
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