Q Chen

Nanjing Medical University, Nanjing, Jiangsu Sheng, China

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Publications (3)17.89 Total impact

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    ABSTRACT: Class A scavenger receptor (SR-A) is primarily expressed in microglia/macrophages and plays an important role in immune responses. However, whether SR-A can influence microglia/macrophage polarization in cerebral ischemic injury is not known. To this end we monitored the phenotypic alteration of microglia/macrophages in an animal model of cerebral ischemia injury. SR-A was up-regulated in mouse brains 24h after permanent occlusion of middle cerebral artery (MCAO). SR-A-deficient mice displayed reduced infarct size and improved neurological function compared with wild-type mice littermate controls. Furthermore, a decrease in inflammatory F4/80(+)CD11b(+)CD45(high)CD11c(+) microglia/macrophages and attenuated nuclear factor-kappaB (NF-κB) activation was found in ischemic brains in the SR-A null mice. This was accompanied by alleviation of classically activated M1 macrophage markers and preservation of alternatively activated M2 macrophage markers. These data suggest that SR-A contributes to cerebral ischemic injury by pivoting the phenotype of microglia/macrophages to a skewed M1 polarization.
    Neuroscience 05/2012; 218:35-48. · 3.12 Impact Factor
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    ABSTRACT: We aimed to evaluate the effect of the mutant Wld(S) (slow Wallerian degeneration; also known as Wld) gene in experimental diabetes on early experimental peripheral diabetic neuropathy and diabetic retinopathy. The experiments were performed in four groups of mice: wild-type (WT), streptozotocin (STZ)-induced diabetic WT, C57BL/Wld(S) and STZ-induced diabetic C57BL/Wld(S). In each group, intraperitoneal glucose and insulin tolerance tests were performed; blood glucose, glycated haemoglobin and serum insulin were monitored. These mice were also subjected to the following behavioural tests: grasping test, hot-plate test and von Frey aesthesiometer test. For some animals, sciatic-tibial motor nerve conduction velocity, tail sensory nerve conduction velocity and eye pattern electroretinogram were measured. At the end of the experiments, islets were isolated to detect glucose-stimulated insulin secretion, ATP content and extent of apoptosis. The NAD/NADH ratio in islets and retinas was evaluated. Surviving retinal ganglion cells were estimated by immunohistochemistry. We found that the Wld(S) gene is expressed in islets and protects beta cells against multiple low doses of STZ by increasing the NAD/NADH ratio, maintaining the ATP concentration, and reducing apoptosis. Consistently, significantly higher insulin concentrations, lower blood glucose concentrations, and better glucose tolerance were observed in Wld(S) mice compared with WT mice after STZ treatment. Furthermore, Wld(S) alleviated abnormal sensory responses, nerve conduction, retina dysfunction and reduction of surviving retinal ganglion cells in STZ-induced diabetic models. We provide the first evidence that expression of the Wld(S) gene decreases beta cell destruction and preserves islet function in STZ-induced diabetes, thus revealing a novel protective strategy for diabetic models.
    Diabetologia 09/2011; 54(9):2440-50. · 6.49 Impact Factor
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    ABSTRACT: Cytokines secreted by infiltrating immune cells during atherogenesis modulate vascular remodeling. One exemplary event is the antagonism between transformed growth factor (TGF-beta) and interferon gamma (IFN-gamma) on the transcriptional control of type I collagen gene (COL1A2). Previously we have reported that IFN-gamma up-regulates regulatory factor for X-box B (RFXB) to repress collagen transcription while down-regulates the expression of RFXBSV, a splice variant of RFXB that blocks collagen repression in fibroblasts. Here we demonstrate that TGF-beta abrogated COL1A2 repression by IFN-gamma through altering the relative expression of RFXB and RFXBSV. Unlike RFXB, RFXBSV did not bind to the collagen promoter and competed with RFXB for the co-repressor histone deacetylase 2 (HDAC2), limiting HDAC2 recruitment to the collagen transcription start site as evidenced by chromatin immunoprecipitation assays. Over-expression of RFXB by lentiviral infection in HASMCs enhanced HDAC2 enlistment, promoted histone deacetylation surrounding the collagen site by IFN-gamma, and blocked the TGF-beta antagonism, a pattern reversed by RFXBSV infection. On the contrary, silencing of RFXB, but not both RFXB and RFXBSV, expression promoted the TGF-beta antagonism. Thus, we have identified a novel mechanism whereby TGF-beta antagonizes the IFN-gamma repression of collagen transcription in HASMCs and as such provided new insights into antiatherogenic strategies.
    Nucleic Acids Research 01/2009; 37(13):4393-4406. · 8.28 Impact Factor