Endothelial progenitor cells (EPCs) have important effect in tissue repair in ischemic organs. The present study was conducted to demonstrate the mobilization of EPCs and its possible mechanism after acute ischemic stroke (AIS). A total of 148 individuals were examined, including 106 patients with ischemic stroke and 42 healthy controls. Seventy-one patients with imaging-confirmed AIS were examined at days 1, 7, 14, and 21 after stroke onset. Circulating EPCs were quantified by flow cytometry using CD133 and KDR surface markers. Serum stromal cell-derived factor-1 (SDF-1) concentrations were determined by enzyme-linked immunosorbent assay. Patients with AIS had significantly lower EPC level than that in the controls (0.022 ± 0.013 vs 0.051 ± 0.020; p < 0.01). This difference did not remain significant after adjusting for risk factors at multivariate analysis. Blood pressure, triglyceride, low-density lipoprotein (LDL), and fasting blood sugar were inversely correlated with EPC levels (p < 0.01). Systolic blood pressure and LDL remained independent predictors of baseline EPC levels. The number of circulating EPCs increased on day 7 after AIS, reached a peak on day 14, and decreased on day 21. The concentration of SDF-1 had similar changes. The increment of EPCs was correlated with the infarct volume (r = 0.708; p = 0.006) and SDF-1 concentration on day 14 (r = 0.714; p < 0.001). Baseline EPC level in patients with AIS reflects the cumulative vascular endothelial damage. EPCs could be mobilized into peripheral circulation in response to stroke stress. This mobilization was associated with the increased expression of SDF-1.

Alzheimer's disease (AD) is pathologically characterized by senile plaques and neurofibrillary tangles composed of β-amyloid peptide (Aβ) and tau hyperphosphorylation, respectively. Mannosylation, a particular type of post-translational modification, may be involved in the pathogenesis of AD. However, its underlying mechanism remains unclear. Protein O-linked mannose β 1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the formation of the N-acetylglucosamine β-1,2-Man linkage of O-mannosylglycan, which can increase the protein post-translational mannosylation level. The defective POMGnT1 gene leads to the hypomannosylation of proteins, which may cause cognitive decline in aged people. This study aimed to investigate whether POMGnT1 participated in the pathogenesis of AD and explore its underlying role using AD mouse and cell models. In this study, the expression of POMGnT1 was measured in AD models [β-amyloid precursor protein (APP)/presenilin-1 (PS1) transgenic mice, an AD mouse model; N2a cells stably transfected with Swedish mutant APP (N2a/APP), an AD cell model]. The results revealed that the expression of POMGnT1 decreased in AD mouse and cell models. Additionally, POMGnT1-overexpressing N2a/APP cells were built by retroviral transfection. POMGnT1 overexpression may lower Aβ levels by reducing APP production and downregulating β-and γ-secretase activities. It also promoted clearance of Aβ by upregulating insulin-degrading enzymes and ameliorated tau hyperphosphorylation. Hence, it was concluded that POMGnT1 was involved in the pathogenic process of AD. The decreased expression of POMGnT1 contributes to AD-like pathologies.

IntroductionProtein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) is crucial for the elongation of O-mannosyl glycans. Mutations in POMGNT1 cause muscle-eye-brain (MEB) disease, one of the main features of which is anatomical aberrations in the brain. A growing number of studies have shown that defects in POMGNT1 affect neuronal migration and distribution, disrupt basement membranes, and misalign Cajal-Retzius cells. Several studies have examined the distribution and expression of POMGNT1 in the fetal or neonatal brain for neurodevelopmental studies in the mouse or human brain. However, little is known about the neuroanatomical distribution and expression of POMGNT1 in the normal adult mouse brain.MethodsWe analyzed the expression of POMGNT1 mRNA and protein in the brains of various neuroanatomical regions and spinal cords by western blotting and RT-qPCR. We also detected the distribution profile of POMGnT1 in normal adult mouse brains by immunohistochemistry and double-immunofluorescence.ResultsIn the present study, we found that POMGNT1-positive cells were widely distributed in various regions of the brain, with high levels of expression in the cerebral cortex and hippocampus. In terms of cell type, POMGNT1 was predominantly expressed in neurons and was mainly enriched in glutamatergic neurons; to a lesser extent, it was expressed in glial cells. At the subcellular level, POMGNT1 was mainly co-localized with the Golgi apparatus, but expression in the endoplasmic reticulum and mitochondria could not be excluded.DiscussionThe present study suggests that POMGNT1, although widely expressed in various brain regions, may has some regional and cellular specificity, and the outcomes of this study provide a new laboratory basis for revealing the possible involvement of POMGNT1 in normal physiological functions of the brain from a morphological perspective.