Mechanism of miR-381 on macrophage infiltration in polymyositis by targeting stromal cell derived actor-1 / 解剖学报

Objective To explore the mechanism of miR-381 on the infiltration of polymyositis (PM) macrophages by targeting stromal cell derived factor-1 (SDF-1). Methods PM model mouse was constructed by rabbit myosin (1.5 mg), mycobacterium tuberculosis (5 mg) and pertussis toxin (500 ng). The 30 PM model mice were divided into control group and PM+miR-381 group (n = 15/group). During the same period, 15 healthy mice were used as a control group. Mice in the PM+miR-381 group were injected with miR-381 agomir (300 μg) intraperitoneally for 2 weeks. Serum creatine kinase (s-CK), interleukin (IL)-1β and IL-6 levels in serum of each group of mice, and the pathological changes of muscle tissue were detected and compared. The macrophage marker protein F4/80 was detected by immunohistochemical staining to assess the infiltration of macrophages. The expression levels of miR-381 and SDF-1 mRNA and protein in muscle tissues of each group were detected. The target relationship between miR-381 and SDF-1 was verified by dual luciferase report. Mouse macrophages were divided into miR-381 NC group and miR-381 mimic group. The SDF-1 mRNA and protein levels in each group were detected by Real-time PCR and Western blotting. Transwell was used to detect the level of cell migration to evaluate the infiltration capacity. Results The above indicators of the three groups were significantly different (P<0.05). The level of miR-381 in the muscle tissue of the PM group was significantly lower than that of the control group, s-CK, IL-1β, IL-6, histological score, macrophage infiltration, and SDF-1 mRNA and protein expression levels were significantly higher than those of the control group (P<0.05). The level of miR-381 in the muscle tissue of the PM+ miR-381 group was significantly higher than that of the PM group, s-CK, IL-1β, IL-6, histological score, macrophage infiltration, and SDF-1 mRNA and protein expression levels were significantly lower than those in the PM group (P<0.05). The dual luciferase report result indicated that miR-381 could target binding to SDF-1. The expression levels of SDF-1 mRNA and protein in macrophages in the miR-381 mimic group were significantly lower than those in the miR-381 NC group (P<0.05). The number of migrating cells in the miR-381 mimic group was significantly lower than that in the miR-381 NC group (P<0.05). Conclusion Increasing the level of miR-381 can inhibit the inflammatory infiltration ability of macrophages by targeting the expression of SDF-1, thereby alleviating PM.

Influence of Different Dietary Salt Concentration on the Renal Fibrosis and Macrophages Infiltration in Salt Sensitive Hypertension / 现代生物医学进展

Objective:To investigate the influence of different salt concentration on the renal fibrosis and macrophages infiltration in salt sensitive hypertension.Methods:Dahl salt sensitive rats were randomly divided into the normal salt (0.3 ％ nacl) group,4 ％ high salt,8 ％ high salt groups at six weeks continuously feeding for 8 weeks,each group contained 15 rats.Tail-cuffmethod was used to value rat blood pressure at 8 weeks,Masson trichromatic method was used to detect renal fibrosis of the three groups at 8 week.Immunohistochemistry and Western blot method were used to depict the renal macrophage infiltration at 8 week.Results:1) The blood pressure of 4 ％ salt and 8％ high salt group rats were significantly higher than those of the normal salt group at 8week,meanwhile the blood pressure of 8 ％ high salt was further increased than that of 4 ％ high salt group at 8 week.2) The relative kidney weight and renal fibrosis of 4 ％ salt and 8 ％ high salt group rats were obviously higher than that of normal salt group at 8week,meanwhile the relative kidney weight and renal fibrosis of 8 ％ high salt were further increased than those of 4 ％ high salt group at 8 week.3) The macrophage infiltration of 4 ％ salt and 8％ high salt group rats were higher than that of the normal salt group at 8week,meanwhile the macrophage infiltration of 8 ％ high salt was further increased than that of 4 ％ high salt group at 8 week.Conclusion:Different high salt concentrations had different effect on the renal fibrosis and macrophage infiltration in the salt sensitive hypertension,high salt concentration could exacerbate the renal fibrosis and macrophage infiltration.

Glucagon-like peptide 1 improves insulin resistance in vitro through anti-inflammation of macrophages

Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.

Smoking-Related Renal Histologic Injury in IgA Nephropathy Patients

PURPOSE: Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. RESULTS: Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. CONCLUSION: In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.

The current development of heme oxygenase-1 and its correlation with macrophage infiltration in adipose tissue of obese individuals / 国际儿科学杂志

Obesity is mostly recognized as a chronic inflammatory condition in which the balance of normal state is destroyed and it is a risk of cardiovascular disease and many other chronic metabolic disease.Heme oxygenase-1 (HO-1),a major cytoprotective enzyme,exerts significant antioxidant and anti-inflammatory effects.It also can improve the function of fat cells and enhanced insulin sensitivity in obese individuals.The researches of HO-1 for the anti-inflammatory effects and its intervention have great significance in improving the inflammatory state and its related diseases in obesity.This paper elaborates the change of HO-1 and its effect for macrophage infiltration in obesity.