Biology subjects

Lee, H. R.

Publications and source records attributed to Lee, H. R..

3 recordsLinked to original sources

bioRxiv2021

TET1 controls Cxcl1 induction by DNA demethylation and promotes neutrophil recruitment during acute lung injury

Neutrophils are rapidly recruited from the peripheral blood to the inflammatory site to initiate inflammatory response against pathogenic infections. The process to recruit neutrophils must be properly regulated since the abnormal accumulation of neutrophils can cause organ damage and dysfunction. The acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a common cause of respiratory failure that is characterized by the infiltration of neutrophils and epithelial integrity disruption. Indeed, recent studies suggest a pathogenic role of neutrophils in the clinic severity of the coronavirus disease 2019 (COVID-19) ARDS. The chemokine CXCL1, which is rapidly induced by inflammatory stimuli, plays a key role in neutrophil influx during lung inflammation. The molecular basis of Cxcl1 induction is not fully understood. Here we report that TET1, a member of the ten eleven translocation (TET) methylcytosine dioxygenase protein family, displays a striking specificity in the regulation of gene expression in macrophages. RNA sequencing (RNA-seq) analysis showed that Tet1 disruption significantly altered the expression of only 48 genes that include Cxcl1 and several other genes known to be important for cell migration and trafficking in bone marrow derived macrophages (BMDMs) in response to LPS stimulation. TET1 regulates the induction of Cxcl1 by facilitating the DNA demethylation of the Cxcl1 promoter. In Tet1-/- mice, the induction of Cxcl1 was suppressed, resulting in defective neutrophil recruitment to the lung during LPS-induced acute lung injury. Our results identify a novel epigenetic mechanism that selectively controls Cxcl1 induction and neutrophil recruitment during acute lung injury. Key PointsO_LITET1 has a striking specificity in macrophage gene regulation and controls Cxcl1 induction by inflammatory stimuli via DNA demethylation C_LIO_LINeutrophil recruitment is defective in Tet1 deficient mice during acute lung injury C_LI

immunology↗

bioRxiv2021

Evaluation of wound healing effects of ginsenoside Rg1 and red ginseng extract in STZ-induced diabetic wound model: an in vivo pilot study

Red ginseng is an immune-enhancing compound that exhibits anti-inflammatory action. The ginsenoside Rg1, an ingredient of red ginseng, has been shown to play an important role in tumor suppression, wound healing, and angiogenesis. This study evaluated the effects of red ginseng extract and Rg1 in a diabetic wound model. Diabetes was induced with streptozotocin (STZ) in 8-week-old male Institute of Cancer Research (ICR) mice weighing 30-35 g. A full-thickness skin defect was treated by applying a dressing every 3 days. The mice were divided into three groups. Group 1 was administered an extract of red ginseng (10 mg/kg/d, n = 27, oral) and group 2 was administered Rg1 (10 mg/kg/d, n = 27, oral). Group 3 was a control group treated with phosphate-buffered saline (0.3 mL/kg/d, n = 27, oral). Red ginseng extract and Rg1 were orally administered to mice daily for 10 days following injury in groups 1 and 2, respectively. Both increased mRNA and protein levels of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-{beta}1 compared to controls. In addition, the wounds of animals in the Rg1 group were significantly smaller between days 7 and 10 (p < 0.05). VEGF and TGF-{beta}1 were not expressed in diabetic mice in the control group. Both red ginseng extract and Rg1 promoted the production of VEGF and TGF-{beta}1, which are important in wound healing. Our results for Rg1 suggest its potential to promote diabetic wound healing by stimulating the production or activity of VEGF and TGF-{beta}1 factors involved in the wound healing process.

molecular biology↗

bioRxiv2020

Kv1.2 contributes to pattern separation by regulating the hippocampal CA3 neuronal ensemble size

Kv1.2 expression in rodent CA3 pyramidal cells (CA3-PC) is polarized to distal apical dendrites, and regulate the synaptic responses to perforant pathway (PP) inputs. Accordingly, Kv1.2 haploinsufficiency (Kcna2+/-) in CA3-PCs, but not Kv1.1 (Kcna1+/-), lowered the threshold for long-term potentiation at PP-CA3 synapses. The Kcna2+/- mice, but not Kcna1+/-, displayed impairments in contextual fear discrimination task. The size and overlap of CA3 ensembles activated by the first visits to slightly different contexts were not different between wildtype and Kcna2+/- mice, but these ensemble parameters diverged over training days between genotypes, suggesting abnormal plastic changes in the CA3 network of Kcna2+/- mice. Eventually, the Kcna2+/- mice exhibited larger ensemble size and overlap upon retrieval of two contexts, compared to wildtype or Kcna1+/- mice. These results suggest that Kv1.2 subunits prevent promiscuous plastic changes at PP-CA3 synapses, and contribute to sparse representation of memories and pattern separation in the CA3 network.

neuroscience↗