Effects of C-C motif chemokine receptor 2 on phenotypic transformation of cardiac fibroblasts after hypoxia / 解放军医学杂志

Objective To investigate the effect of C-C motif chemokine receptor 2 (CCR2) on phenotypic transformation of cardiac fibroblasts after hypoxia. Methods The mouse myocardium primary fibroblasts were extracted by collagenase digestion. Cells were divided into control, hypoxia-24h and hypoxia-48h, the mRNA and protein expression of CCR2 was examined by real-time PCR and Western blotting. CCR2 low expression cell (si-CCR2) was established using by small interfering RNA. Cells were divided into four groups including si-control, si-CCR2, si-control+hypoxia, si-CCR2+hypoxia. The mRNA and protein expressions of CCR2, α smooth muscle actin (α-SMA) and Collagen 1A (Col 1A) were detected by real-time PCR and Western blotting, cell proliferation was detected by Cell Counting Kit-8 (CCK8) and Bromodeoxyuridine (BrdU). Results Compared with control, the mRNA and protein levels of CCR2 significantly increased in hypoxia-24h and hypoxia-48h group (P<0.01), however, no significance was found in these two time points. Compared with si-control group, the mRNA and protein expressions of CCR2, α-SMA and Col 1A not significantly changed in si-CCR2 group. Compared with si-control group, the mRNA and protein levels of CCR2, α-SMA and Col 1A significantly increased in si-control+hypoxia group (P<0.01 or P<0.05), and cell proliferation increased (P<0.01). Compared with si-control+hypoxia group, the protein expression of α-SMA and Col 1A decreased in si-CCR2+hypoxia group (P<0.05), and cell proliferation also decreased in si-CCR2+hypoxia group (P<0.05). Conclusions CCR2 could affect the phenotypic transformation of cardiac fibroblasts after hypoxia.

Evaluation on three short-term animal models of alcoholic liver disease / 药学学报

Alcoholic liver disease (ALD) includes a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis and cirrhosis. According to epidemical statistics, ALD has been ranked as the second major cause of liver diseases in China. Many animal models have been made in the study of potential therapies. However, in most of the models, the pathological changes are not always consistent with those in patients. There are three widely used short-term animal models of ALD:the acute alcoholic liver injury model, Gao-binge steatohepatitis model and CCl4-alcohol diet induced liver fibrosis model. In this study, we evaluated the pathological responses of these models and compared the responses with the clinical parameters. The liver/body weight ratio was increased and liver histological lesions were induced in alcoholic groups in the three models, while the levels of biochemical parameters and inflammatory factors were affected by different type of treatments. In the acute alcoholic model, the mRNA levels of interleukin-6 (IL-6) and C-C motif chemokine receptor-2 (CCL2) were surprisingly decreased, which was consistent with the transcriptome profile in patients (P P IL-6 and CCL2 (P CCL2 was impacted differently at various stages of ALDs, which can be considered as a potential biomarker.

The role of C-C motif chemokine ligand 2 in respiratory diseases / 国际儿科学杂志

C-C motif chemokine ligand 2 (CCL2),one of the most widely studied chemokines,plays an important role in tissue damage and repair in many inflammatory diseases.Inflammation occurs when CCL2 mainly through the identification and combined with its specific receptor CCR2,the inflammatory signal into the nucleus to activate nuclear transcription factor,and ultimately activates and raises monocytes / macrophages to the inflammatory site.This article reviews the latest advances in chemokine CCL2 in respiratory diseases,which provides new ideas for clinical diagnosis,treatment and prognosis.

Chemokine Systems Link Obesity to Insulin Resistance

Obesity is a state of chronic low-grade systemic inflammation. This chronic inflammation is deeply involved in insulin resistance, which is the underlying condition of type 2 diabetes and metabolic syndrome. A significant advance in our understanding of obesity-associated inflammation and insulin resistance has been recognition of the critical role of adipose tissue macrophages (ATMs). Chemokines are small proteins that direct the trafficking of immune cells to sites of inflammation. In addition, chemokines activate the production and secretion of inflammatory cytokines through specific G protein-coupled receptors. ATM accumulation through C-C motif chemokine receptor 2 and its ligand monocyte chemoattractant protein-1 is considered pivotal in the development of insulin resistance. However, chemokine systems appear to exhibit a high degree of functional redundancy. Currently, more than 50 chemokines and 18 chemokine receptors exhibiting various physiological and pathological properties have been discovered. Therefore, additional, unidentified chemokine/chemokine receptor pathways that may play significant roles in ATM recruitment and insulin sensitivity remain to be fully identified. This review focuses on some of the latest findings on chemokine systems linking obesity to inflammation and subsequent development of insulin resistance.