Gwang Hyeon Eom

Chonnam National University · Department of Pharmacology

The regeneration of myocardium following acute circulatory events remains a challenge, despite numerous efforts. Mesenchymal stem cells (MSCs) present a promising cell therapy option, but their differentiation into cardiomyocytes is a time-consuming process. Although it has been demonstrated that PSME4 degrades acetyl-YAP1, the role of PSME4 in the...

We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF...

Intensive research has focused on minimizing the infarct area and stimulating endogenous regeneration after myocardial infarction. Our group previously elucidated that apicidin, a histone deacetylase (HDAC) inhibitor, robustly accelerates the cardiac commitment of naïve mesenchymal stem cells (MSCs) through acute loss of YAP1. Here, we propose the...

Intensive research has focused on minimizing the infarct area and stimulating endogenous regeneration after myocardial infarction. Our group elucidated that apicidin, a histone deacetylase (HDAC) inhibitor, robustly stimulates cardiac commitment of mesenchymal stem cells (MSCs) through acute loss of YAP1. Here we further studied the mechanism of th...

Vascular calcification increases morbidity and mortality in patients with cardiovascular and renal diseases. Previously, we reported that histone deacetylase 1 prevents vascular calcification, whereas its E3 ligase, mouse double minute 2 homolog (MDM2), induces vascular calcification. In the present study, we identified the upstream regulator of MD...

Heat shock protein (HSP) 70 is a molecular chaperone that regulates protein structure in response to thermal stress. In addition, HSP70 is involved in post-translational modification and is related to the severity of some diseases. Here, we tested the functional relevance of long-lasting HSP70 expression in a model of nonischemic heart failure usin...

Background: Basic studies suggest that statins as add-on therapy may benefit patients with COVID-19; however, real-world evidence of such a beneficial association is lacking. Objective: We investigated differences in SARS-CoV-2 test positivity and clinical outcomes of COVID-19 (composite endpoint: admission to intensive care unit, invasive venti...

Higher-order chromatin structure regulates gene expression, and mutations in proteins mediating genome folding underlie developmental disorders known as cohesinopathies. However, the relationship between three-dimensional genome organization and embryonic development remains unclear. Here we define a role for bromodomain-containing protein 4 (BRD4)...

Diagnosis of Kawasaki disease (KD) is occasionally delayed because it is solely based on clinical symptoms. Previous studies have attempted to identify diagnostic biomarkers for KD. Recently, patients with KD were reported to have elevated serum ferritin levels. We investigated the usefulness of the serum ferritin level as a diagnostic biomarker fo...

BACKGROUND Basic studies suggest that statins as add-on therapy may benefit patients with COVID-19; however, real-world evidence of such a beneficial association is lacking. OBJECTIVE We investigated differences in SARS-CoV-2 test positivity and clinical outcomes of COVID-19 (composite endpoint: admission to intensive care unit, invasive ventilati...

Background: Although the clinical importance of heart failure with preserved ejection fraction (HFpEF) has been extensively explored, most therapeutic regimens, including nitric oxide (NO) donors, lack therapeutic benefit. Although the clinical characteristics of HFpEF are somewhat heterogeneous, diastolic dysfunction (DD) is one of the most import...

Cancer remains a leading cause of death, despite multimodal treatment approaches. Even in patients with a healthy immune response, cancer cells can escape the immune system during tumorigenesis. Cancer cells incapacitate the normal cell-mediated immune system by expressing immune modulation ligands such as programmed death (PD) ligand 1, the B7 mol...

The clinical importance of heart failure with preserved ejection fraction (HFpEF) has recently become apparent. HFpEF refers to heart failure (HF) symptoms with normal or near-normal cardiac function on echocardiography. Common clinical features of HFpEF include diastolic dysfunction, reduced compliance, and ventricular hypokinesia. HFpEF differs f...

The current study was undertaken to investigate whether histone deacetylases (HDACs) can modulate the viability of retinal ganglion cells (RGCs) and the activity of glial cells in a mouse model of retinal ischemia-reperfusion (IR) injury. C57BL/6J mice were subjected to constant elevation of intraocular pressure for 60 min to induce retinal IR inju...

Mesenchymal stem cells (MSCs) can suppress pathological inflammation. However, the mechanisms underlying the association between MSCs and inflammation remain unclear. Under coculture conditions with macrophages, MSCs highly expressed angiopoietin-like 4 (ANGPTL4) to blunt the polarization of macrophages toward the proinflammatory phenotype. ANGPTL4...

Heart failure refers to an inappropriate blood supply to the periphery. Among subtype of heart failure, pathophysiology and effective therapeutic strategy of systolic heart failure is well established. However, molecular mechanism and specific regimens for diastolic heart failure (DHF) still remains unclear. Here we propose nitric oxide synthase (N...

Although the clinical importance of heart failure with preserved ejection fraction (HFpEF), which makes up half of heart failure, has been extensively explored, most therapeutic regimens, including nitric oxide (NO) donors, lack therapeutic benefit. Here we report that neuronal nitric oxide synthase (nNOS, also known as NOS1) induces HFpEF by S-nit...

Fibrosis is characterized by excessive deposition of the extracellular matrix and develops because of fibroblast differentiation during the process of inflammation. Various cytokines stimulate resident fibroblasts, which differentiate into myofibroblasts. Myofibroblasts actively synthesize an excessive amount of extracellular matrix, which indicate...

After the publication of this article, the authors noticed an error in one of the grant numbers (2015R1A2A1A05001708) in the Acknowledgements section.

The novel histone deacetylase inhibitor CG200745 was initially developed to treat various hematological and solid cancers. We investigated the molecular mechanisms associated with the renoprotective effects of CG200745 using deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats. DOCA strips (200 mg/kg) were implanted into rats one week af...

Heart failure indicates that heart is ultimately unable to pump enough blood for the whole body. The mortality rate due to ischemic heart disease has not changed dramatically, but that for heart failure has risen steeply. However, molecular mechanism of development of heart failure is not fully elucidated. We combined the microarray results of hear...

Aims: Previously, we reported that phosphorylation of histone deacetylase (HDAC) 2 and the resulting activation causes cardiac hypertrophy. Through further study of the specific binding partners of phosphorylated HDAC2 and their mechanism of regulation, we can better understand how cardiac hypertrophy develops. Thus, in the present study, we aimed...

Obesity is associated with various human disorders, such as type 2 diabetes, cardiovascular diseases, hypertension, and cancers. In this study, we observed that knockout (KO) of CCN5, which encodes a matricellular protein, caused mild obesity in mice. The CCN5 KO mice also exhibited mild diabetes characterized by high fasting glucose levels and imp...

mRNA expression levels of CCN5. (A) Relative expression of CCN5 in total RNA extracted from organs of WT, CCN5 hetero KO (+/−), and CCN5 KO (−/−) (n = 2 per group). (B) Relative mRNA expression of CCN5 in total RNA extracted from hearts of WT and CCN5 KO mice after completing 24 weeks on a NCD or HFD (n = 4–5 per group). Data are presented as mean...

Histological analysis of fibrotic area in adipose tissues. (A) Representative images and (B) quantitative data for Masson’s trichrome staining of adipose tissue sections from WT and CCN5 KO mice. Data are presented as mean ± SD. *p<0.05, **p<0.01 vs. WT. (EPS)

Food intake, water intake, and HbA1c percentage. (A) Mean daily food intake and water intake over 5 days after 22 weeks on NCD or HFD feeding (mean data collected from three experimental sets, n = 6–12 per group for each individual experimental set). (B) HbA1c percentage after 24 weeks on NCD or HFD feeding (n = 4–6/group). Data are presented as me...

Western blot analysis of insulin signaling molecules in isolated cardiomyocytes. Western blot analysis of insulin signaling molecules in isolated adult mouse cardiomyocytes after treatment with human insulin (100 nM) for various periods of time. (B) Original uncropped blot images. Blots marked with protein sizes were used for analysis (blots not ma...

Lipids in plasma and cardiac cells. (DOCX)

Doppler’s Echocardiographic data. (DOCX)

Primer sequences for quantitative rear-time PCR. (DOCX)

Background: Adriamycin (ADR) is a powerful chemotherapeutic agent extensively used to treat various human neoplasms. However, its clinical utility is hampered due to severe adverse side effects i.e. cardiotoxicity and heart failure. ADR-induced cardiomyopathy (AIC) has been reported to be caused by myocardial damage and dysfunction through oxidati...

Tubulointerstitial fibrosis is a common feature of kidney disease. Histone deacetylase (HDAC) inhibitors have been reported to attenuate renal fibrosis progression. Here, we investigated the effect of CG200745, a novel HDAC inhibitor, on renal fibrosis development in a mouse model of unilateral ureteral obstruction (UUO). To examine the effects of...

A regulatory mechanism that controls how cardiac muscle responds to stress could inform development of new therapies for preventing heart failure. Physiological stimuli ranging from heavy exercise to heart attack can induce hypertrophy, an increase in cardiac muscle mass that is initially beneficial but can lead to organ failure. Researchers led by...

Purpose: To investigate whether histone deacetylase (HDAC) activity is associated with postoperative scarring and to evaluate the effect of HDAC inhibition by topical trichostatin A (TSA) on conjunctival fibrosis after trabeculectomy in a rat model. Methods: Trabeculectomy was performed on the left eye of Sprague-Dawley rats. In the first experi...

Background: Kawasaki disease (KD) is known as systemic vasculitis, and more than half of the patients with KD have myocarditis, which can induce ventricular dysfunction. In this study, we evaluate left ventricular (LV) dysfunction in patients with KD based on the myocardial performance index (MPI) using pulse Doppler (PD) and tissue Doppler imagin...

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentia...

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of SUMO modification during myogenesis have not been fully elucidated. Here we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated m...

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited C...

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV), features loss of pain sensation, decreased or absent sweating (anhidrosis), recurrent episodes of unexplained fever, self-mutilating behavior and variable mental retardation. Mutations in neurotrophic receptor tyrosi...

S100 calcium-binding protein A4 (S100A4) induces proliferation and migration of vascular smooth muscle cells (VSMCs). We aimed to find the microRNA regulating S100A4 expression. S100A4 transcripts are abruptly increased in the acute phase of carotid arterial injury one day later (at day 1) but gradually decreases at days 7 and 14. Bioinformatics an...

Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation e...

Rationale: Cardiac hypertrophy is an adaptive process to meet the hemodynamic demands from exogenous stresses, and histone deacetylase (HDAC) 2 plays central role in cardiac remodeling. Recently, we have suggested the importance of acetylation of HDAC2; however, specific phosphatase of HDAC2 remains unclear. Objective: We aimed to delineate the pho...

Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction, and even transcription. HDACs are also post-transcriptional modifiers that regulate the protein acetylation implicated in several pathophysiologic states. HDAC inhibitors have been highlighted as a novel category o...

Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation e...

Supplementary Figures 1-9

Skeletal muscle atrophy results from the net loss of muscular proteins and organelles and is caused by pathologic conditions such as nerve injury, immobilization, cancer, and other metabolic diseases. Recently, ubiquitination-mediated degradation of skeletal-muscle-specific transcription factors was shown to be involved in muscle atrophy , although...

Vascular calcification (VC) often associates with many cardiovascular and metabolic diseases. Although VC is the cause of high morbidity and mortality, molecular mechanisms have yet to be elucidated. Here we report that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity enhanced VC in vivo and in vitro...

Rationale: Cardiac hypertrophy is an adaptation for increased hemodynamic demands by underlying diseases and histone deacetylase (HDAC) 2 phosphorylation and following its activation are closely associated with those of process. Recently, we have demonstrated that the acetylation of HDAC2 K75 could induce S394 phosphorylation; however, specific mec...

The fine balance between proliferation and differentiation of vascular smooth muscle cells (VSMCs) is indispensable for the maintenance of healthy blood vessels, whereas an increase in proliferation participates in pathologic cardiovascular events such as atherosclerosis and restenosis. Here we report that microRNA-34c (miR-34c) targets stem cell f...

Cardiac hypertrophy is a form of global remodeling, though its initial step seems to be an adaptation to the increased hemodynamic demands. The characteristics of cardiac hypertrophy include the functional reactivation of arrested fetal gene program, where histone deacetylases (HDACs) are closely linked in the development of the process. To date, m...

Posttranslational modification (PTM) is a term that implies dynamic modification of proteins after their translation. PTM is involved not only in homeostasis but also in pathologic conditions related to diverse diseases. Histone deacetylases (HDACs), which are known as transcriptional regulators, are one example of posttranslational modifiers with...

Rationale: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA binding domain. By interacting with other transcription factors, SHP regulates diverse biological events including glucose metabolism in liver. The role of SHP in adult heart diseases has not yet been demonstrated. Objective: We ai...

Rationale: Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of the class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear. Objective: Recently, we suggested that casein kinase-2α1-dependent phosphory...

Skeletal muscle atrophy results from the net loss of muscular proteins and organelles and is caused by pathologic conditions such as nerve injury, immobilization, cancer, and other metabolic diseases. Recently, ubiquitination-mediated degradation of skeletal-muscle-specific transcription factors was shown to be involved in muscle atrophy, although...

Rationale: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA-binding domain. Through interactions with other transcription factors, SHP regulates diverse biological events, including glucose metabolism in liver. However, the role of SHP in adult heart diseases has not yet been demonstrated....

Histone deacetylases (HDACs) are closely involved in cardiac reprogramming. Although the functional roles of the class I and class IIa HDACs are well established, the significance of interclass crosstalk in the development of cardiac hypertrophy remains unclear. Recently, we suggested that casein kinase-2α1-dependent phosphorylation of HDAC2 leads...

Estrogen-related receptor gamma (ERRγ) is an orphan nuclear receptor that has biological roles mainly in metabolism and that controls metabolic switching in perinatal heart. In adult heart diseases, however, the functional roles of ERRγ have not yet been elucidated. In the present study, we aimed to characterize the role of ERRγ in cardiac hypertro...

The proliferation and remodeling of vascular smooth muscle cells (VSMCs) is an important pathological event in atherosclerosis and restenosis. Here we report that microRNA-132 (miR-132) blocks vascular smooth muscle cells (VSMC) proliferation by inhibiting the expression of LRRFIP1 [leucine-rich repeat (in Flightless 1) interacting protein-1]. Micr...

Introduction— Estrogen-related receptor gamma (ERRγ) is an orphan nuclear receptor that has biological roles mainly in metabolism and it controls metabolic switching in perinatal heart. In adult heart diseases, however, the functional roles of ERRγ have not yet been elucidated. Hypothesis— In the present study, we aimed to characterize the role of...

Background: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor lacking DNA binding domain. SHP directly modulates the activities of other nuclear receptors and regulates a variety of cellular events such as cell differentiation, proliferation, and metabolism in various tissues. However, the role of SHP in heart has not ye...

Although the right ventricular (RV) myocardial performance index (MPI) usually is increased in the presence of RV dysfunction and pressure overload, debate continues over the correlation between the RV MPI and functional derangement in patients with RV pressure-overload congenital heart disease (CHD). To address this controversy, this study took se...

Histone lysine methylation and demethylation are considered critical steps in transcriptional regulation. In this report, we performed chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis to examine the genome-wide occupancy of H3K9-me2 during all-trans-retinoic acid (ATRA)-induced differentiation of HL-60 promyelocytic leu...

Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that regulates a variety of cellular events such as cell proliferation, differentiation and metabolism in liver and bone. However, the role of SHP in heart has not yet been elucidated. In this study, we investigated the functional roles of SHP in cardiac hypertrophy. In r...

Background. Cardiac hypertrophy is characterized by transcriptional reprogramming of fetal gene expression, and histone modifiers are tightly linked to the regulation of those genes. We previously reported that activation of histone deacetylase (HDAC) 2, one of the class I HDACs, mediates hypertrophy. Here we suggest that disinhibiting of kruppel-l...

Histone lysine methylation, as one of the most important factors in transcriptional regulation, is associated with a various physiological conditions. Using a bioinformatics search, we identified and subsequently cloned mouse SET domain containing 3 (SETD3) with SET (Su(var)3-9, Enhancer-of-zeste and Trithorax) and Rubis-subs-bind domains. SETD3 is...

Skeletal myogenesis is precisely regulated by multiple transcription factors. Previously, we demonstrated that enhancer of polycomb 1 (Epc1) induces skeletal muscle differentiation by potentiating serum response factor (SRF)-dependent muscle gene activation. Here, we report that an interacting partner of Epc1, ret finger protein (RFP), blocks skele...

Cardiac hypertrophy is characterized by transcriptional reprogramming of fetal gene expression, and histone deacetylases (HDACs) are tightly linked to the regulation of those genes. We previously demonstrated that activation of HDAC2, 1 of the class I HDACs, mediates hypertrophy. Here, we show that casein kinase-2α1 (CK2α1)-dependent phosphorylatio...

Although right ventricular hypertrophy (RVH) is an adaptive process to stresses such as outflow tract obstruction, uncorrected persistent RVH often results in failure of the right ventricle or even the left ventricle. Histone deacetylase (HDAC) inhibitors can effectively prevent or block left ventricular hypertrophy, so the present study compared t...

A family of PRDM proteins are similar to histone methyltransferases (HMTases) with SET domain in that they modulate different cellular processes, including transcriptional regulation, through chromatin modifying activities. By applying a bioinformatic approach, we searched for proteins containing the SET domain and identified a double zinc-finger d...

Skeletal muscle differentiation is well regulated by a series of transcription factors. We reported previously that enhancer of polycomb1 (Epc1), a chromatin protein, can modulate skeletal muscle differentiation, although the mechanisms of this action have yet to be defined. Here we report that Epc1 recruits both serum response factor (SRF) and p30...

Diverse cardiac diseases induce cardiac hypertrophy, which leads to dilatation and heart failure. We previously reported that hypertrophy can be blocked by class I histone deacetylase (HDAC) inhibitor, which prompted us to investigate the regulatory mechanism of class I HDACs. Cardiac hypertrophy was introduced by aortic banding, by infusion of iso...

Histone methylation is crucial for transcriptional regulation and chromatin remodeling. It has been suggested that the SET domain containing protein RE-IIBP (interleukin-5 [IL-5] response element II binding protein) may perform a function in the carcinogenesis of certain tumor types, including myeloma. However, the pathogenic role of RE-IIBP in the...

Evolutionary conserved SET domains were originally identified in three Drosophila proteins: suppressor of variegation (Su (var) 3-9), enhancer of zeste (E(z)), and the trithorax. Some of the SET-domain containing proteins have been known to elicit methylation of histone lysine residues. Based on a search for SET-domain containing proteins using bio...

The autosomal dominant giant platelet syndromes (GPS), characterized by triads of giant platelets, thrombocytopenia, and Döhle-like leukocyte inclusions are caused by MYH9 mutation, a gene encoding the nonmuscle myosin heavy chain-IIA. This study was aimed to identify the Korean GPS patients and to define clinical findings and molecular characteris...

Autosomal dominant GPS is characterized by thrombocytopenia, giant platelets and Doehle-like inclusion bodies. Studies have indicated that platelet structure and function are normal, suggesting a defect in megakaryocyte fragmentation. This study was aimed to identify Korean patients with GPS and define clinical findings and molecular characteristic...