MG53 protects against contrast-induced acute kidney injury by reducing cell membrane damage and apoptosis.

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 µg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.

Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis.

Irisin, a myokine, is cleaved from the extracellular portion of fibronectin domain-containing 5 protein in skeletal muscle and myocardium and secreted into circulation as a hormone during exercise. Irisin has been found to exert protective effects against lung and heart injuries. However, whether irisin influences myocardial infarction (MI) remains unclear. In this study we investigated the therapeutic effects of irisin in an acute MI model and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for 2 weeks after MI. Cardiac function was assessed using echocardiography. We found that irisin administration significantly alleviated MI-induced cardiac dysfunction and ventricular dilation at 4 weeks post-MI. Irisin significantly reduced infarct size and fibrosis in post-MI hearts. Irisin administration significantly increased angiogenesis in the infarct border zone and decreased cardiomyocyte apoptosis, but did not influence cardiomyocyte proliferation. In human umbilical vein endothelial cells (HUVEC), irisin significantly increased the phosphorylation of ERK, and promoted the migration of HUVEC detected in wound-healing and transwell chamber migration assay. The effects of irisin were blocked by the ERK inhibitor U0126. In conclusion, irisin improves cardiac function and reduces infarct size in post-MI mouse heart. The therapeutic effect is associated with its pro-angiogenic function through activating ERK signaling pathway.

[Effects of lipid-modulation and antiplatelet treatment on the endothelial lipase expression].

OBJECTIVE: To investigate the effects of lipid-modulation and antiplatelet treatment on the expression of endothelial lipase (EL) of patients with coronary artery disease (CAD), and investigate the role of EL in the development of CAD. METHODS: One hundred and fifty-seven cases were divided into three groups according to clinical manifestations and the results of coronary artery angiography: control group (n=41) with more than one risk factors of CAD and the vessel lesions was <30%; stable angina pectoris (SAP) group (n=55); acute coronary syndrome (ACS) group (n=61). The EL positive cell rate was measured 2 weeks after cessation of lipid-modulation and aspirin treatment, and 6 months after treatment with simvastatin and/or aspirin. The drug was ceased for the complications or not tolerance for the treatment. RESULTS: Except the patients in control group with aspirin treatment, the EL positive cell rate was significantly decreased among other groups [control group with simvastatin: (3.93±0.87)% vs. (5.28±1.05)%, SAP group: (8.16±2.11)% vs. (15.12±2.53)%, ACS group: (13.93±3.22)% vs. (38.44±4.36)%; SAP group with aspirin: (10.57±4.07)% vs. (14.66±2.29)%, ACS group: (18.28±5.14)% vs. (40.27±3.96)%; control group with aspirin and simvastatin: (3.13±0.87)% vs. (5.33±1.25)%, SAP group: (5.68±2.20)% vs. (14.89±2.15)%, ACS group: (7.81±3.96)% vs. (39.27±5.17)%, P<0.05 or P<0.01]. CONCLUSION: The treatment with lipid-modulation and/or antiplatelet drug may significantly decrease the expression of EL, implying that EL participates in the progression of CAD.

[G protein kinase 4gammaA142V overexpression induced hypertension by downregulating D1 receptors in transgenic mice].

OBJECTIVE: Abnormalities in dopamine production and receptor function have been described in human essential hypertension and rodent models of genetic hypertension. We investigated the role of G protein kinase (GRK) 4gamma in essential hypertension in GRK4gamma mutant A142V transgenic mice. METHODS: Blood pressure, renal sodium excretion, D(1) receptor protein expression and phosphorylation were measured in GRK4gammaA142V transgenic mice and control mice. Moreover, the effects of GRK4 inhibition by antisense oligonucleotides on D(1) receptor expressions were determined in HK-2 cells. RESULTS: As compared with their control mice, GRK4gammaA142V transgenic mice had higher blood pressure, lower D(1) receptor expression (0.6 +/- 0.2 vs. 1.5 +/- 0.2, P < 0.05), higher D(1) receptor phosphorylation [(65 +/- 7) DU vs. (35 +/- 7) DU, P < 0.05] in renal cortical membranes and the diuretic and natriuretic effects after stimulation of renal D(1) receptor were impaired in GRK4gammaA142V transgenic mice. Inhibition of GRK4 expression (0.60 +/- 0.10 vs. 1.30 +/- 0.09, P < 0.05) by GRK4 antisense oligonucleotides upregulated D(1) receptor expression (1.5 +/- 0.2 vs. 0.8 +/- 0.1, P < 0.05) in HK-2 cells. CONCLUSIONS: Our results show that GRK4gammaA142V overexpression induced hypertension is mediated by dowregulated renal D(1) receptor expressions in GRK4gammaA142V transgenic mice.