Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation and inflammatory processes play a major role in myocardial IR injury. Netrin-1 is a laminin-related protein identified as a neuronal guidance cue and netrin-1 expressed outside the nervous system inhibits migration of leukocytes in vitro and in vivo and attenuates inflammation-mediated tissue injury. In our study, hearts of C57BL/6 mice were flushed and stored in cold Bretschneider solution for 8 h and then transplanted into syngeneic recipient. We found that netrin-1 decreased cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24 h after myocardial IR injury was reduced by netrin-1 administration. Cardiac output at 60 mmHg of afterload pressure was significantly increased in hearts with netrin-1 administration (IR + Netrin-1: 59.9 ± 5.78 ml/min; IR: 26.2 ± 4.3 ml/min; P < 0.05). Netrin-1 treatment increased expression of the alternatively activated macrophage (AAM) markers arginase-1 (Arg-1) and mannose receptor (MR) and promoted proliferator-activated receptor γ (PPARγ) expression in cardiac allograft. Furthermore, decreased TnT expression and reduced allograft infiltration of neutrophils and monocytes/macrophages by netrin-1 was abolished with addition of PPARγ antagonist. In conclusion, netrin-1 attenuates cardiac IR injury and generates AAM which contributes to the protective effect of netrin-1.

Serum chemerin level during the first trimester of pregnancy has the potential to predict risk of GDM.

Chemerin is a cytokine that attracts much attention in the reproductive process. This study aimed to explore the effects of chemerin and its receptor chemokine-like receptor 1 (CMKLR1) on the maintenance of early pregnancy. The expression levels of chemerin and CMKLR1 in the decidua tissues of 20 early normal pregnant women and 20 early spontaneous abortion women were examined byWestern blot and real-time polymerase chain reaction analyses. CMKLR1 receptor antagonist (α-NETA) was then intrauterinely injected into normal pregnant mice model to assess its effect on the outcome of pregnancy and the phosphorylation rate of ERK1/2 in decidua tissues.We found that the expression level of chemerin in women who had experienced early spontaneous abortion was lower than in those who had experienced normal early pregnancy (P < 0.01); conversely, CMKLR1 expression was higher in the former than in the latter (P < 0.01). In a pregnant-mouse model, the embryo resorption rate of α-NETA group was higher than that in the negative control group (61.5% vs. 10.8%) (P < 0.001). Compared with the control group, ERK1/2 phosphorylation in decidua tissues decreased in the α-NETA-treated group (P < 0.01). These results suggested that the inhibition of the chemerin/CMKLR1 signaling pathway can lead to the abortion of mouse embryos, and that chemerin/CMKLR1 may play an important role in the maintenance of early pregnancy possibly by regulating ERK1/2 phosphorylation.