Boxiong Deng

All Publications

• Induction of a Müller glial-specific protective pathway safeguards the retina from diabetes induced damage. Diabetes Lin, C. H., Wu, M. R., Tanasa, B., Prakhar, P., Deng, B., Davis, A. E., Li, L., Xia, A., Shan, Y., Fort, P. E., Wang, S. 2024

  Abstract

  Diabetes can lead to cell-type-specific responses in the retina, including vascular lesions, glial dysfunction and neurodegeneration, all of which contribute to retinopathy. However, the molecular mechanisms underlying these cell type-specific responses, and the cell types that are sensitive to diabetes have not been fully elucidated. Employing single cell transcriptomics, we profiled the transcriptional changes induced by diabetes in different retinal cell types in rat models as the disease progressed. Rod photoreceptors, a subtype of amacrine interneurons, and Müller glia exhibited rapid responses to diabetes at the transcript levels. Genes associated with ion regulation were upregulated in all three cell types, suggesting a common response to diabetes. Furthermore, focused studies revealed that while Müller glia initially increased the expression of genes playing protective roles, they cannot sustain this beneficial effect. We explored one of the candidate protective genes, Zinc finger protein 36 homolog (Zfp36), and observed that depleting Zfp36 in rat Müller glial cells in vivo using AAV-based tools exacerbated diabetes-induced phenotypes, including glial reactivation, neurodegeneration, and vascular defects. Over-expression of Zfp36 slowed the development of these phenotypes. This work unveiled retinal cell types that are sensitive to diabetes and demonstrated that Müller glial cells can mount protective responses through Zfp36.

  View details for DOI 10.2337/db24-0199

  View details for PubMedID 39446557

• Employing plasmid-based CRISPR-hyperdCas12, CasRx, and prime editing systems for in vivo gene manipulation in the mouse retina Li, L., Hamed, L., Liu, Z., Deng, B., Sun, Y., Wang, S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001313316207295

• Prevention of DSS-induced colitis in mice with water kefir microbiota via anti-inflammatory and microbiota-balancing activity. Food & function Ye, Z., Yang, X., Deng, B., Liao, Z., Fang, X., Wang, J. 2023; 14 (15): 6813-6827

  Abstract

  Water kefir, a natural and stable functional microbiota system consisting of a symbiotic mixture of probiotics, shows multiple bioactivities but little is known about the effect of water kefir microbiota on the prevention of inflammatory bowel disease (IBD), which is one of the most common intestinal problems and has become a worldwide public health concern. Here, the main objectives of the present study were to investigate the preventative effects of water kefir microbiota, a probiotic consortium mainly consisting of bacteria belonging to Acetobacter, Lactobacillus, and Komagataeibacter and fungi belonging to Saccharomyces and Talaromyces, in a dextran sodium sulfate (DSS)-induced colitis mouse model and unveil the underlying mechanism of the action. Water kefir microbiota effectively improved the disease severity of DSS-induced colitis, including decreased body weight and colon length, increased spleen index and DAI score, and colonic tissue damage. Moreover, water kefir microbiota restored the abnormal expression of tight junction proteins (such as occludin, ZO-1, and claudin-1) and pro-inflammatory and anti-inflammatory cytokines (such as IL-1β, IL-6, TNF-α, COX-2, iNOS, and IL-10) and inactivated TLR4-MyD88-NF-κB pathway induced by DSS. Water kefir microbiota also improved the composition and metabolism of intestinal microbiota. These findings demonstrated that water kefir microbiota could exert protective roles in the DSS-induced colitis mouse model by reducing inflammation and regulating microbial dysbiosis, which will be helpful for the development of water kefir microbiota-based microbial products as an alternative preventative strategy for IBD.

  View details for DOI 10.1039/d3fo00354j

  View details for PubMedID 37449473

• PDGFD switches on stem cell endothelial commitment. Angiogenesis Lu, W., Xu, P., Deng, B., Zhang, J., Zhan, Y., Lin, X., Xu, X., Xia, Z., Yang, X., Zeng, X., Huang, L., Xie, B., Wang, C., Wang, S., Kuang, H., Han, X., Mora, A., Cao, Y., Jiang, Q., Li, X. 2022; 25 (4): 517-533

  Abstract

  The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.

  View details for DOI 10.1007/s10456-022-09847-4

  View details for PubMedID 35859222

  View details for PubMedCentralID PMC9519648

• Platelet-derived growth factor C signaling is a potential therapeutic target for radiation proctopathy. Science translational medicine Lu, W., Xie, Y., Huang, B., Ma, T., Wang, H., Deng, B., Zou, S., Wang, W., Tang, Q., Yang, Z., Li, X., Wang, L., Fang, L. 2021; 13 (582)

  Abstract

  Radiation proctopathy (RP) is characterized by inflammation of colorectal tissue and is a common complication of radiation therapy for pelvic malignancies with high incidence but lacking effective treatment. Here, we found that platelet-derived growth factor C (PDGF-C) and fibrosis markers were up-regulated in tissue samples from patients with RP and in rectal tissues after irradiation in a mouse model of RP. Genetic deletion of Pdgf-c in mice ameliorated RP-induced injuries. Genome-wide gene expression profiling and in vitro assays revealed that the promotive effect of PDGF-C in RP development was mediated by activation of PDGF receptors (PDGFRs) and C-X-C motif chemokine receptor 4, a proinflammatory chemokine regulated by transcription factor ETS variant transcription factor 1. Treatment with crenolanib, a selective inhibitor of PDGFRs, prevented or reduced RP in mice after irradiation. These results reveal that inhibition of PDGF-C signaling may have therapeutic value for the treatment of RP.

  View details for DOI 10.1126/scitranslmed.abc2344

  View details for PubMedID 33627485

• Human Embryonic Stem Cell-Derived Cardiovascular Progenitors Repair Infarcted Hearts Through Modulation of Macrophages via Activation of Signal Transducer and Activator of Transcription 6. Antioxidants & redox signaling Wang, J., Liu, M., Wu, Q., Li, Q., Gao, L., Jiang, Y., Deng, B., Huang, W., Bi, W., Chen, Z., Chin, Y. E., Paul, C., Wang, Y., Yang, H. T. 2019; 31 (5): 369-386

  Abstract

  Aims: Human embryonic stem cell derived-cardiovascular progenitor cells (hESC-CVPCs) are a promising cell source for cardiac repair, while the underlying mechanisms need to be elucidated. We recently observed cardioprotective effects of human pluripotent stem cell (hPSC)-CVPCs in infarcted nonhuman primates, but their effects on inflammation during early phase of myocardial infarction (MI) and the contribution of such effect to the cardioprotection are unclear. Results: Injection of hESC-CVPCs into acutely infarcted myocardium significantly ameliorated the functional worsening and scar formation, concomitantly with reduced inflammatory reactions and cardiomyocyte apoptosis as well as increased vascularization. Moreover, hESC-CVPCs modulated cardiac macrophages toward a reparative phenotype in the infarcted hearts, and such modulation was further confirmed in vitro using human cardiovascular progenitor cell (hCVPC)-conditioned medium (hCVPC-CdM) and highly contained interleukin (IL)-4/IL-13. Furthermore, signal transducer and activator of transcription 6 (STAT6) was activated in hCVPC-CdM- and IL-4/IL-13-treated macrophages in vitro and in hESC-CVPC-implanted MI hearts, resulting in the polarization of macrophages toward a reparative phenotype in the post-MI hearts. However, hESC-CVPC-mediated modulation on macrophages and cardioprotection were abolished in STAT6-deficient MI mice. Innovation: This is the first report about the immunoregulatory role played by hESC-CVPCs in the macrophage polarization in the infarcted hearts, its importance for the infarct repair, and the underlying signaling pathway. The findings provide new insight into the mechanism of microenvironmental regulation of stem cell-based therapy during acute MI. Conclusions: Implantion of hESC-CVPCs during the early phase of MI promotes infarct repair via the modulation of macrophage polarization through secreted cytokine-mediated STAT6 activation. The findings suggest a therapeutic potential by modulating macrophage polarization during acute phase of MI.

  View details for DOI 10.1089/ars.2018.7688

  View details for PubMedID 30854870

  View details for PubMedCentralID PMC6602123