Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy

Shang, Jin; Wang, Luyao; Zhang, Ya Ping; Zhang, Shiyi; Ning, Lina; Zhao, Jifang; Cheng, Genyang; Liu, Dong; Xiao, Jing; Zhao, Zhanzheng

doi:10.1111/jcmm.14237

Cited by 42 publications

(39 citation statements)

References 37 publications

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“…It has been reported that, in the kidney of diabetic animal model, the expression of CMKLR1 was gradually upregulated with the progression of renal dysfunction [35]. Knockdown of CMKLR1 ameliorated renal damage and inflammation in DN mice [36]. Recent studies showed that CMKLR1 was activated by Wnt/beta-catenin pathway which is involved in accumulation of extracellular matrix (ECM), podocyte dysfunction, and renal fibrosis in DN [37–39].…”

Section: Discussionmentioning

confidence: 99%

Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes

Wang

Yao

et al. 2019

International Journal of Endocrinology

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Objective. Type 2 diabetes (T2DM) is a global epidemic and increases mortality due to its vascular complications. Chemerin has been found to exert a major role in glucose and lipid metabolism. The aim of this study was to explore the correlation between plasma chemerin levels and microangiopathy in patients with T2DM. Methods. A total of 598 T2DM patients were classified into two groups: with and without microvascular complications. Anthropometric parameters and blood pressure were taken. The amounts of glycosylated hemoglobin, glucose, lipid profiles, creatinine, and chemerin concentrations in the blood were determined. The presence and severity of nephropathy, retinopathy, and neuropathy were also evaluated by specific tests. Results. Plasma levels of chemerin in diabetic subjects with microvascular complications were markedly elevated compared to those without. The number of microvascular complications increased with high plasma chemerin levels. Patients with high chemerin levels had an increased incidence of nephropathy and retinopathy. Furthermore, the chemerin plasma concentrations increased with the progression of diabetic nephropathy with highest values in macroalbuminuria groups. In contrast, no significant difference was observed in plasma chemerin levels between subjects with and without peripheral neuropathy. Pearson correlation analysis showed that plasma chemerin levels were positively related to duration of diabetes, serum creatinine, and 24-hour urine albumin excretion, even after multiple adjustments. Using logistic regression analysis, plasma chemerin concentrations were independently associated with the presence of nephropathy and retinopathy, not neuropathy. Conclusion. This study elucidated a positive correlation between increased chemerin levels and the development of some subtypes of diabetic microangiopathy.

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Section: Discussionmentioning

confidence: 99%

Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes

Wang

Yao

et al. 2019

International Journal of Endocrinology

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“…In human VSMCs, chemerin has pro-apoptotic, pro-inflammatory, and proliferative effects that are mediated by nicotinamide adenine dinucleotide phosphate oxidase (Nox) activation and redox-sensitive mitogen-activated protein kinases signalling [ 136 ]. In glomerular endothelial cells, chemerin treatment increases the secretion of the pro-inflammatory cytokines TNFα, IL-6, IL-8, and TGF-β1, and exposure to high concentrations of glucose increases the mRNA levels of both chemerin and CMKLR1 in these cells [ 137 ]. However, an anti-inflammatory effect of chemerin in endothelial cells by the inhibition of NF-κB, the TNF-α-induced adhesion of monocytes, and the oxidised low-density lipoprotein (oxLDL)-induced macrophage foam cell formation has also been described, as was a reduction in the presence of pro-inflammatory markers [ 86 , 113 ].…”

Section: Role Of Some Adipokines In Inflammatory Processes Associamentioning

confidence: 99%

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Feijóo‐Bandín

Aragón-Herrera

Moraña-Fernández

et al. 2020

IJMS

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It is well established that adipose tissue, apart from its energy storage function, acts as an endocrine organ that produces and secretes a number of bioactive substances, including hormones commonly known as adipokines. Obesity is a major risk factor for the development of cardiovascular diseases, mainly due to a low grade of inflammation and the excessive fat accumulation produced in this state. The adipose tissue dysfunction in obesity leads to an aberrant release of adipokines, some of them with direct cardiovascular and inflammatory regulatory functions. Inflammation is a common link between obesity and cardiovascular diseases, so this review will summarise the role of the main adipokines implicated in the regulation of the inflammatory processes occurring under the scenario of cardiovascular diseases.

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“…Long-term exposure to HG levels induces glomerular endothelial cell inflammation and injury [7]. Different inflammatory molecules, including chemokines, adhesion molecules, and proinflammatory cytokines, are critical factors that may be involved in diabetic nephropathy [8].…”

Section: Introductionmentioning

confidence: 99%

Gene Regulatory Effect of Pyruvate Kinase M2 is Involved in Renal Inflammation in Type 2 Diabetic Nephropathy

Tang

Yang

et al. 2020

Exp Clin Endocrinol Diabetes

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Background and Aims The inflammation of glomerular endothelial cells induces and promotes the activation of macrophages and contributes to the development of diabetic nephropathy. Thus, this study aimed to investigate the gene regulatory effect and potential role of pyruvate kinase M2 (PKM2) in inflammatory response in diabetic nephropathy. Methods The plasma PKM2 levels of patients with diabetes were evaluated. Eight-week-old mice were divided into three groups (WT, db/db mice, and db/db mice treated with TEPP-46) and raised for 12 weeks. Blood and kidney samples were collected at the end of the experiment. Endothelial cells were stimulated with high glucose with or without TEPP-46. The expression of intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), interleukin 1 beta (IL-1β), phospho-PKM2, PKM2, phospho-STAT3, STAT3, nuclear factor kappa B (NF-kB), and phospho-NF-kB in vivo and in vitro were determined using Western blot. The activation of macrophages (CD68+CD86+) in the glomeruli was assessed via fluorescent double staining. Moreover, immune endothelial adhesion experiments were performed. Results The plasma PKM2 levels of patients with type 2 diabetes increased. P-PKM2 was up-regulated in vivo and in vitro. TEPP-46 decreased inflammatory cell infiltration and ICAM-1 expression in vivo and in vitro and inhibited the differentiation of macrophages to M1 cells in db/db mice with diabetic nephropathy. PKM2 regulated the phosphorylation of STAT3 and NF-kB. Furthermore, high glucose levels induced the transition from tetramer to dimer and the nuclear translocation of PKM2. Conclusion The gene regulatory effect of PKM2 is involved in renal inflammation in type 2 diabetic nephropathy by promoting the phosphorylation of STAT3 and NF-kB and the expression of intercellular adhesion molecule 1. Thus, the down-regulation of phosphorylated PKM2 may have protective effects against diabetic nephropathy by inhibiting renal inflammation.

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Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy

Cited by 42 publications

References 37 publications

Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes

Increased Circulating Chemerin in Relation to Chronic Microvascular Complications in Patients with Type 2 Diabetes

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Gene Regulatory Effect of Pyruvate Kinase M2 is Involved in Renal Inflammation in Type 2 Diabetic Nephropathy

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