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  • Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity Nature Immunology Liu, Q., Johnson, E., et al 2019
  • bFGF-Regulating MAPKs Are Involved in High Glucose-Mediated ROS Production and Delay of Vascular Endothelial Cell Migration PLOS ONE Zhu, Z. X., Cai, W. H., Wang, T., Ye, H. B., Zhu, Y. T., Chi, L. S., Duan, Y. M., Sun, C. C., Xuan, Y. H., Jin, L. T. 2015; 10 (12)

    Abstract

    High blood sugar is a symptom of diabetes mellitus (DM). Vascular endothelial cells (VECs) directly contact the blood and are damaged when blood sugar levels are high. However, the molecular mechanism underlying this process remains elusive. To analyze the effects of DM on migration, we simulated DM by applying high glucose (HG) to the human VEC. HG delayed cell migration and induced phosphorylation of MAPKs (JNK and ERK). By contrast, in presence of bFGF, cell migration was promoted and MAPK phosphorylation levels were reduced. Furthermore, treatment with JNK and ERK inhibitors rescued HG-mediated delay of cell migration. Molecular and cell biological studies demonstrated that HG increased ROS production, whereas treatment with bFGF or JNK/ERK inhibitors blocked HG-induced ROS accumulation. Addition of MnTMPyP, a ROS scavenger, reduced HG-induced ROS production and accelerated cell migration, suggesting that the influence of HG on bFGF-MAPK signaling causes accumulation of ROS, which in turn regulate cell migration. This is the first study to elucidate the molecular mechanism of HG-mediated VEC migration; these findings could facilitate the development of novel therapies for DM.

    View details for DOI 10.1371/journal.pone.0144495

    View details for Web of Science ID 000366902700134

    View details for PubMedID 26642060

    View details for PubMedCentralID PMC4671674

  • High-Glucose Inhibits Human Fibroblast Cell Migration in Wound Healing via Repression of bFGF-Regulating JNK Phosphorylation PLOS ONE Xuan, Y. H., Bin Huang, B., Tian, H. S., Chi, L. S., Duan, Y. M., Wang, X., Zhu, Z. X., Cai, W. H., Zhu, Y. T., Wei, T. M., Ye, H. B., Cong, W. T., Jin, L. T. 2014; 9 (9)

    Abstract

    One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.

    View details for DOI 10.1371/journal.pone.0108182

    View details for Web of Science ID 000343679800074

    View details for PubMedCentralID PMC4171528

  • Overexpression of a SNARE protein AtBS14b alters BR response in Arabidopsis BOTANICAL STUDIES Zhu, Z. X., Ye, H. B., Xuan, Y. H., Yao, D. N. 2014; 55

    Abstract

    N-ethyl-maleimide sensitive factor adaptor protein receptor (SNAREs) domain-containing proteins were known as key players in vesicle-associated membrane fusion. Genetic screening has revealed the function of SNAREs in different aspects of plant biology, but the role of many SNAREs are still unknown. In this study, we have characterized the role of Arabidopsis Qc-SNARE protein AtBS14b in brassinosteroids (BRs) signaling pathway.AtBS14b overexpression (AtBS14b ox) plants exhibited short hypocotyl and petioles lengths as well as insensitivity to exogenously supplied BR, while AtBS14b mutants did not show any visible BR-dependent morphological differences. BR biosynthesis enzyme BR6OX2 expression was slightly lower in AtBS14b ox than in wild type plants. Further BR-mediated repression of BR6OX2, CPD and DWF4 was inhibited in AtBS14b ox plants. AtBS14b-mCherry fusion protein localized in vesicular compartments surrounding plasma membrane in N. benthamiana leaves. In addition, isolation of AtBS14b-interacting BR signaling protein, which localized in plasma membrane, showed that AtBS14b directly interacted with membrane steroid binding protein 1 (MSBP1), but did not interact with BAK1 or BRI1.These data suggested that Qc-SNARE protein AtBS14b is the first SNARE protein identified that interacts with MSBP1, and the overexpression of AtBS14b modulates BR response in Arabidopsis.

    View details for DOI 10.1186/s40529-014-0055-5

    View details for Web of Science ID 000347373100001

    View details for PubMedCentralID PMC5430330

  • Overexpression of a SNARE protein AtBS14b alters BR response in Arabidopsis. Botanical studies Zhu, Z. X., Ye, H. B., Xuan, Y. H., Yao, D. N. 2014; 55 (1): 55

    Abstract

    N-ethyl-maleimide sensitive factor adaptor protein receptor (SNAREs) domain-containing proteins were known as key players in vesicle-associated membrane fusion. Genetic screening has revealed the function of SNAREs in different aspects of plant biology, but the role of many SNAREs are still unknown. In this study, we have characterized the role of Arabidopsis Qc-SNARE protein AtBS14b in brassinosteroids (BRs) signaling pathway.AtBS14b overexpression (AtBS14b ox) plants exhibited short hypocotyl and petioles lengths as well as insensitivity to exogenously supplied BR, while AtBS14b mutants did not show any visible BR-dependent morphological differences. BR biosynthesis enzyme BR6OX2 expression was slightly lower in AtBS14b ox than in wild type plants. Further BR-mediated repression of BR6OX2, CPD and DWF4 was inhibited in AtBS14b ox plants. AtBS14b-mCherry fusion protein localized in vesicular compartments surrounding plasma membrane in N. benthamiana leaves. In addition, isolation of AtBS14b-interacting BR signaling protein, which localized in plasma membrane, showed that AtBS14b directly interacted with membrane steroid binding protein 1 (MSBP1), but did not interact with BAK1 or BRI1.These data suggested that Qc-SNARE protein AtBS14b is the first SNARE protein identified that interacts with MSBP1, and the overexpression of AtBS14b modulates BR response in Arabidopsis.

    View details for PubMedID 28510978

    View details for PubMedCentralID PMC5430330

  • High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. PloS one Xuan, Y. H., Huang, B. B., Tian, H. S., Chi, L. S., Duan, Y. M., Wang, X., Zhu, Z. X., Cai, W. H., Zhu, Y. T., Wei, T. M., Ye, H. B., Cong, W. T., Jin, L. T. 2014; 9 (9)

    Abstract

    One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.

    View details for DOI 10.1371/journal.pone.0108182

    View details for PubMedID 25244316

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