Fibroblast growth factor 10 protects neuron against oxygen-glucose deprivation injury through inducing heme oxygenase-1.

Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen-glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000 ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V+PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke.

MicroRNAs in the regulation of immune response against infections.

Innate immunity is considered to provide the initial defense against infections by viruses, bacteria, fungi, and protozoa. Detection of the signature molecules of invading pathogens by front-line defense cells via various germline-encoded pattern recognition receptors (PRRs) is needed to activate intracellular signaling cascades that lead to transcriptional expression of inflammatory mediators to coordinate the elimination of pathogens and infected cells. To maintain a fine balance between protective immunity and inflammatory pathology upon infection, the innate signaling pathways in the host need to be tightly regulated. MicroRNAs (miRNAs), a new class of small non-coding RNAs, have been recently shown to be potent modulators that function at post-transcriptional levels. Accumulating evidence demonstrates that the involvement of microorganism-encoded and host miRNAs might play instructive roles in the immune response upon infection. Here, we discuss the current knowledge of miRNAs in the regulation of immune response against infections.

Glutamine-induced heat shock protein protects against renal ischaemia-reperfusion injury in rats.

AIM: To find out if a single dose of glutamine can relieve acute renal ischaemia-reperfusion injury in rats, to explore the role of heat shock protein in this process. METHODS: Forty-eight Sprague-Dawley rats were assigned to four groups: saline as control group; glutamine group; quercetin (heat shock protein inhibitor) plus glutamine group; and quercetin plus saline group. The renal ischaemia-reperfusion rat model was established 1 h after drug administration. Serum creatinine (CR) and blood urea nitrogen (BUN) were analyzed. The kidneys were harvested to evaluate the degree of renal injuries. Heat shock protein expression was detected by immunohistochemistry and western blot. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and apoptosis index was calculated. RESULTS: Statistical data from CR, BUN, haematoxylin-eosin (HE) dyeing and TUNEL assay results showed that ischaemia-reperfusion injury and cell apoptosis in the glutamine group were significantly milder than those in control group (P < 0.05), while ischaemia-reperfusion injury and cell apoptosis in the quercetin plus glutamine group and quercetin plus saline group were more severe than those in the control group (P < 0.05). Statistical data from immunohistochemistry and western blot results showed that heat shock protein expression was enhanced in the glutamine group compared with that in the control group (P < 0.01), while it was weaker in the quercetin plus glutamine group and quercetin plus saline group than that in the control group (P < 0.01). CONCLUSION: Our experiment suggested that a single dose of glutamine could relieve renal ischaemia-reperfusion injury in rats in 24 h, and its mechanism may be associated with enhanced heat shock protein expression. This finding may provide a new alternative for protecting against clinical renal ischaemia-reperfusion injury.