1.Hormonal Regulation of Hematopoietic Stem Cells and Their Niche: A Focus on Estrogen.
Hye Ryeon HEO ; Li CHEN ; Borim AN ; Kye Seong KIM ; Junfeng JI ; Seok Ho HONG
International Journal of Stem Cells 2015;8(1):18-23
Self-renewal and differentiation are hallmarks of stem cells and controlled by various intrinsic and extrinsic factors. Increasing evidence indicates that estrogen (E2), the primary female sex hormone, is involved in regulating the proliferation and lineage commitment of adult and pluripotent stem cells as well as modulating the stem cell niche. Thus, a detailed understanding of the role of E2 in behavior of stem cells may help to improve their therapeutic potential. Recently, it has been reported that E2 promotes cell cycle activity of hematopoietic stem and progenitor cells and induces them to megakaryocyte-erythroid progenitors during pregnancy. This study paves the way towards a previously unexplored endocrine mechanism that controls stem cell behavior. In this review, we will focus on the scientific findings regarding the regulatory effects of E2 on the hematopoietic system including its microenvironment.
Adult
;
Cell Cycle
;
Estrogens*
;
Female
;
Hematopoiesis
;
Hematopoietic Stem Cells*
;
Hematopoietic System
;
Humans
;
Megakaryocyte-Erythroid Progenitor Cells
;
Pluripotent Stem Cells
;
Pregnancy
;
Stem Cell Niche
;
Stem Cells
2.Inhibition of voltage-dependent K+ channels by antimuscarinic drug fesoterodine in coronary arterial smooth muscle cells
Seojin PARK ; Minji KANG ; Ryeon HEO ; Seo-Yeong MUN ; Minju PARK ; Eun-Taek HAN ; Jin-Hee HAN ; Wanjoo CHUN ; Hongzoo PARK ; Won Sun PARK
The Korean Journal of Physiology and Pharmacology 2022;26(5):397-404
Fesoterodine, an antimuscarinic drug, is widely used to treat overactive bladder syndrome. However, there is little information about its effects on vascular K+ channels. In this study, voltage-dependent K+ (Kv) channel inhibition by fesoterodine was investigated using the patch-clamp technique in rabbit coronary artery. In whole-cell patches, the addition of fesoterodine to the bath inhibited the Kv currents in a concentration-dependent manner, with an IC50 value of 3.19 ± 0.91 μM and a Hill coefficient of 0.56 ± 0.03. Although the drug did not alter the voltage-dependence of steady-state activation, it shifted the steady-state inactivation curve to a more negative potential, suggesting that fesoterodine affects the voltage-sensor of the Kv channel. Inhibition by fesoterodine was significantly enhanced by repetitive train pulses (1 or 2 Hz). Furthermore, it significantly increased the recovery time constant from inactivation, suggesting that the Kv channel inhibition by fesoterodine is use (state)-dependent. Its inhibitory effect disappeared by pretreatment with a Kv 1.5 inhibitor. However, pretreatment with Kv2.1 or Kv7 inhibitors did not affect the inhibitory effects on Kv channels. Based on these results, we conclude that fesoterodine inhibits vascular Kv channels (mainly the Kv1.5 subtype) in a concentration- and use (state)-dependent manner, independent of muscarinic receptor antagonism.
3.ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells.
Jae Hoon JEONG ; Jeeyoung KIM ; Jeongwoon KIM ; Hye Ryeon HEO ; Jin Seon JEONG ; Young Joon RYU ; Yoonki HONG ; Seon Sook HAN ; Seok Ho HONG ; Seung Joon LEE ; Woo Jin KIM
Tuberculosis and Respiratory Diseases 2017;80(3):247-254
BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.
Cadmium
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Cytokines
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Environmental Pollutants
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Epithelial Cells*
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Gene Expression
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Gene Expression Profiling
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Humans*
;
Immunohistochemistry
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In Situ Hybridization
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Inflammation
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Lung
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Lung Neoplasms
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Pulmonary Disease, Chronic Obstructive
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RNA, Messenger
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Signal Transduction
;
Smoke
;
Smoking
;
Succinate Dehydrogenase
4.Cadmium-induced ER stress and inflammation are mediated through C/EBP–DDIT3 signaling in human bronchial epithelial cells.
Jeeyoung KIM ; Haengseok SONG ; Hye Ryeon HEO ; Jung Woon KIM ; Hye Ryun KIM ; Yoonki HONG ; Se Ran YANG ; Seon Sook HAN ; Seung Joon LEE ; Woo Jin KIM ; Seok Ho HONG
Experimental & Molecular Medicine 2017;49(9):e372-
Cadmium (Cd), a major component of cigarette smoke, disrupts the normal functions of airway cells and can lead to the development of various pulmonary diseases such as chronic obstructive pulmonary disease (COPD). However, the molecular mechanisms involved in Cd-induced pulmonary diseases are poorly understood. Here, we identified a cluster of genes that are altered in response to Cd exposure in human bronchial epithelial cells (BEAS-2B) and demonstrated that Cd-induced ER stress and inflammation are mediated via CCAAT-enhancer-binding proteins (C/EBP)-DNA-damaged-inducible transcript 3 (DDIT3) signaling in BEAS-2B cells. Cd treatment led to marked upregulation and downregulation of genes associated with the cell cycle, apoptosis, oxidative stress and inflammation as well as various signal transduction pathways. Gene set enrichment analysis revealed that Cd treatment stimulated the C/EBP signaling pathway and induced transcriptional activation of its downstream target genes, including DDIT3. Suppression of DDIT3 expression using specific small interfering RNA effectively alleviated Cd-induced ER stress and inflammatory responses in both BEAS-2B and normal primary normal human bronchial epithelial cells. Taken together, these data suggest that C/EBP signaling may have a pivotal role in the early induction of ER stress and inflammatory responses by Cd exposure and could be a molecular target for Cd-induced pulmonary disease.
Apoptosis
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Cadmium
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CCAAT-Enhancer-Binding Proteins
;
Cell Cycle
;
Down-Regulation
;
Epithelial Cells*
;
Humans*
;
Inflammation*
;
Lung Diseases
;
Oxidative Stress
;
Pulmonary Disease, Chronic Obstructive
;
RNA, Small Interfering
;
Signal Transduction
;
Smoke
;
Tobacco Products
;
Transcriptional Activation
;
Up-Regulation
5.Inhibitory effects of the atypical antipsychotic, clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells
Minji KANG ; Ryeon HEO ; Seojin PARK ; Seo-Yeong MUN ; Minju PARK ; Eun-Taek HAN ; Jin-Hee HAN ; Wanjoo CHUN ; Kwon-Soo HA ; Hongzoo PARK ; Won-Kyo JUNG ; Il-Whan CHOI ; Won Sun PARK
The Korean Journal of Physiology and Pharmacology 2022;26(4):277-285
To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.