Prmt7 is required for the osteogenic differentiation of mesenchymal stem cells via modulation of BMP signaling

Tuan Anh Vuong,Yan Zhang,June Kim,Young-Eun Leem,Jong-Sun Kang 생화학분자생물학회 2024 BMB Reports Vol.57 No.7

Arginine methylation, which is catalyzed by protein argininemethyltransferases (Prmts), is known to play a key role in variousbiological processes. However, the function of Prmts inosteogenic differentiation of mesenchymal stem cells (MSCs)has not been clearly understood. In the current study, weattempted to elucidate a positive role of Prmt7 in osteogenicdifferentiation. Prmt7-depleted C3H/10T1/2 cells or bone marrowmesenchymal stem cells (BMSCs) showed the attenuatedexpression of osteogenic specific genes and Alizarin red stainingcompared to the wild-type cells. Furthermore, we foundthat Prmt7 deficiency reduced the activation of bone morphogeneticprotein (BMP) signaling cascade, which is essential forthe regulation of cell fate commitment and osteogenesis. Takentogether, our data indicate that Prmt7 plays important regulatoryroles in osteogenic differentiation.

SGTb regulates a surface localization of a guidance receptor BOC to promote neurite outgrowth

Vuong, Tuan Anh,Lee, Sang-Jin,Leem, Young-Eun,Lee, Jae-Rin,Bae, Gyu-Un,Kang, Jong-Sun Elsevier 2019 Cellular signalling Vol.55 No.-

<P><B>Abstract</B></P> <P>Neuritogenesis is a critical event for neuronal differentiation and neuronal circuitry formation during neuronal development and regeneration. Our previous study revealed a critical role of a guidance receptor BOC in a neuronal differentiation and neurite outgrowth. However, regulatory mechanisms for BOC signaling pathway remain largely unexplored. In the current study, we have identified Small glutamine-rich tetratricopeptide repeat (TPR)-containing b (SGTb) as a BOC interacting protein through yeast two-hybrid screening. Like BOC, SGTb is highly expressed in brain and P19 embryonal carcinoma (EC) cells differentiated into neuronal cells. BOC and SGTb proteins co-precipitate in mouse brain and differentiated P19 EC cells. Furthermore, BOC and SGTb co-localize in neurites and especially are concentrated at the tip of neurites in various neuronal cells. SGTb depletion attenuates neuronal differentiation of P19 cells through reduction of the surface level of BOC. Additionally, SGTb depletion causes BOC localization at neurite tip, coinciding with decreased p-JNK levels critical for actin cytoskeleton remodeling. The overexpression of SGTb or BOC restores JNK activation in BOC or SGTb-depleted cells, respectively. Finally, SGTb elevates the level of surface-resident BOC in BOC-depleted cells, restoring JNK activation. Taken together, our data suggest that SGTb interacts with BOC and regulates its surface level and consequent JNK activation, thereby promoting neuronal differentiation and neurite outgrowth.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The TPR-region of SGTb is critical for the interaction with the intracellular region of BOC. </LI> <LI> SGTb-BOC was colocalized at the tip of neurites during neuronal differentiation. </LI> <LI> SGTb restores neuronal differentiation and JNK activity in BOC-depleted cells. </LI> <LI> SGTb regulates BOC's localization at the tip of neurite and JNK activation. </LI> <LI> SGTb promotes neurogenesis and neurite outgrowth through BOC-mediated JNK activation. </LI> </UL> </P>

Pt-AlGaN/GaN HEMT-based hydrogen gas sensors with and without SiNx post-passivation

Vuong, Tuan Anh,Kim, Hyungtak Institute of Korean Electrical and Electronics Eng 2019 전기전자학회논문지 Vol.23 No.3

GaN-based sensors have been widely investigated thanks to its potential in detecting the presence of hydrogen. In this study, we fabricated hydrogen gas sensors with AlGaN/GaN heterojunction and investigated how the sensing performance to be affected by SiN surface passivation. The gas sensor employed a high electron mobility transistors (HEMTs) with 30 nm platinum catalyst as a gate to detect the hydrogen presence. SiN layer was deposited by inductively-coupled chemical vapor deposition as post-passivation. The sensors with SiN passivation exhibited hydrogen sensing characteristics with various gas flow rates and concentrations of hydrogen in inert background gas at $200^{\circ}C$ similar to the ones without passivation. Aside from quick response time for both sensors, there are differences in sensitivity and recovery time because of the existence of the passivation layer. The results also confirmed the dependence of sensing performance on gas flow rate and gas concentration.

Pt-AlGaN/GaN HEMT-based hydrogen gas sensors with and without SiNx post-passivation

tuan anh vuong,김형탁 한국전기전자학회 2019 전기전자학회논문지 Vol.23 No.3

GaN-based sensors have been widely investigated thanks to its potential in detecting the presence of hydrogen. In this study, we fabricated hydrogen gas sensors with AlGaN/GaN heterojunction and investigated how thesensing performance to be affected by SiN surface passivation. The gas sensor employed a high electron mobilitytransistors (HEMTs) with 30 nm platinum catalyst as a gate to detect the hydrogen presence. SiN layer wasdeposited by inductively-coupled chemical vapor deposition as post-passivation. The sensors with SiN passivationexhibited hydrogen sensing characteristics with various gas flow rates and concentrations of hydrogen in inertbackground gas at 200 oC similar to the ones without passivation. Aside from quick response time for bothsensors, there are differences in sensitivity and recovery time because of the existence of the passivation layer. The results also confirmed the dependence of sensing performance on gas flow rate and gas concentration.

Characteristics of Immunogenicity against SARS-CoV-2 in a Community-Based Model of Care during the Fourth Wave of COVID-19 Outbreak in Ho Chi Minh City

Lan Ngoc Vuong,Tu Hoang Kim Trinh,Tuan Diep Tran,Duy Le Pham,Vinh Nhu Nguyen,Quan Tran Thien Vu,Toan Duong Pham,Phong Hoai Nguyen,Minh Kieu Le,Diem Dinh Kieu Truong,Vu Anh Hoang,Nghia Huynh,Dat Quoc N 연세대학교의과대학 2024 Yonsei medical journal Vol.65 No.9

Purpose: Although some immune protection from close contact with individuals who have coronavirus disease 2019 (COVID-19) has been documented, there is limited data on the seroprevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals who were in lockdown with confirmed COVID-19 cases. This study investigated immunogenicity against SARS-CoV-2 in household members and people who lived near home-quarantined patients with COVID-19. Materials and Methods: This cross-sectional study was conducted during the community-based care that took place during lockdowns in District 10, Ho Chi Minh City, Vietnam from July to September 2021. SARS-CoV-2 antibody levels were determined in index cases of COVID-19, household contacts, and a no-contact group from the same area. Results: A total of 770 participants were included (355 index cases, 103 household contacts, and 312 no contacts). All index cases were unvaccinated, but >90% of individuals in the household and no-contact groups had received ≥1 vaccine dose. SARS-CoV-2 neutralizing antibodies (Nabs) were present in >77% of unvaccinated index cases versus 64%/65.4% in the household/no-contact groups (p=0.001). Antibody concentrations in unvaccinated index cases were significantly higher than those in household contacts and no contacts, with no difference between the latter groups. In all cases, antibody levels declined markedly ≥6 weeks after infection, and failed to persist beyond this time in the household and no-contact groups. Conclusion: Community-based care may have helped to create community immunogenicity, but Nabs did not persist, highlighting a need for vaccination for all individuals before, or from 6 weeks after, infection with SARS-CoV-2.

Methylation determines the extracellular calcium sensitivity of the leak channel NALCN in hippocampal dentate granule cells

Seul-Yi Lee,Tuan Anh Vuong,Xianlan Wen,Hyeon-Ju Jeong,Hyun-Kyung So,Ilmin Kwon,Jong-Sun Kang,Hana Cho 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

The sodium leak channel NALCN is a key player in establishing the resting membrane potential (RMP) in neurons andtransduces changes in extracellular Ca2+ concentration ([Ca2+]e) into increased neuronal excitability as thedownstream effector of calcium-sensing receptor (CaSR). Gain-of-function mutations in the human NALCN gene causeencephalopathy and severe intellectual disability. Thus, understanding the regulatory mechanisms of NALCN isimportant for both basic and translational research. This study reveals a novel mechanism for NALCN regulation byarginine methylation. Hippocampal dentate granule cells in protein arginine methyltransferase 7 (PRMT7)-deficientmice display a depolarization of the RMP, decreased threshold currents, and increased excitability compared to wildtypeneurons. Electrophysiological studies combined with molecular analysis indicate that enhanced NALCN activitiescontribute to hyperexcitability in PRMT7−/− neurons. PRMT7 depletion in HEK293T cells increases NALCN activity byshifting the dose-response curve of NALCN inhibition by [Ca2+]e without affecting NALCN protein levels. In vitromethylation studies show that PRMT7 methylates a highly conserved Arg1653 of the NALCN gene located in thecarboxy-terminal region that is implicated in CaSR-mediated regulation. A kinase-specific phosphorylation siteprediction program shows that the adjacent Ser1652 is a potential phosphorylation site. Consistently, our data fromsite-specific mutants and PKC inhibitors suggest that Arg1653 methylation might modulate Ser1652 phosphorylationmediated by CaSR/PKC-delta, leading to [Ca2+]e-mediated NALCN suppression. Collectively, these data suggest thatPRMT7 deficiency decreases NALCN methylation at Arg1653, which, in turn, decreases CaSR/PKC-mediated Ser1652phosphorylation, lifting NALCN inhibition, thereby enhancing neuronal excitability. Thus, PRMT7-mediated NALCNinhibition provides a potential target for the development of therapeutic tools for neurological diseases.

PRMT7 deficiency causes dysregulation of the HCN channels in the CA1 pyramidal cells and impairment of social behaviors

Seul-Yi Lee,Tuan Anh Vuong,Hyun-Kyung So,Hyun-Ji Kim,Yoo Bin Kim,Jong-Sun Kang,Ilmin Kwon,Hana Cho 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

HCN channels regulate excitability and rhythmicity in the hippocampal CA1 pyramidal cells. Perturbation in the HCN channel current (Ih) is associated with neuropsychiatric disorders, such as autism spectrum disorders. Recently, protein arginine methyltransferase 7 (PRMT7) was shown to be highly expressed in the hippocampus, including the CA1 region. However, the physiological function of PRMT7 in the CA1 neurons and the relationship to psychiatric disorders are unclear. Here we showed that PRMT7 knockout (KO) mice exhibit hyperactivity and deficits in social interaction. The firing frequency of the CA1 neurons in the PRMT7 KO mice was significantly higher than that in the wild-type (WT) mice. Compared with the WT CA1 neurons, the PRMT7 KO CA1 neurons showed a more hyperpolarized resting potential and a higher input resistance, which were occluded by the Ih-current inhibitor ZD7288; these findings were consistent with the decreased Ih and suggested the contribution of Ih-channel dysfunction to the PRMT7 KO phenotypes. The HCN1 protein level was decreased in the CA1 region of the PRMT7 KO mice in conjunction with a decrease in the expression of Shank3, which encodes a core scaffolding protein for HCN channel proteins. A brief application of the PRMT7 inhibitor DS437 did not reproduce the phenotype of the PRMT7 KO neurons, further indicating that PRMT7 regulates Ih by controlling the channel number rather than the open probability. Moreover, shRNA-mediated PRMT7 suppression reduced both the mRNA and protein levels of SHANK3, implying that PRMT7 deficiency might be responsible for the decrease in the HCN protein levels by altering Shank3 expression. These findings reveal a key role for PRMT7 in the regulation of HCN channel density in the CA1 pyramidal cells that may be amenable to pharmacological intervention for neuropsychiatric disorders.

Inducible Prmt1 ablation in adult vascular smooth muscle leads to contractile dysfunction and aortic dissection

Pyun Jung-Hoon,Ahn Byeong-Yun,Vuong Tuan Anh,Kim Su Woo,조윤주,Jeon Jaehyung,Baek Seung Ho,Kim Jaewon,Park Sungsu,배규운,Choi Jun-Hyuk,Kim Jae-Ryong,Ryu Dongryeol,Lee Sang-Jin,강종순 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

Vascular smooth muscle cells (VSMCs) have remarkable plasticity in response to diverse environmental cues. Although these cells are versatile, chronic stress can trigger VSMC dysfunction, which ultimately leads to vascular diseases such as aortic aneurysm and atherosclerosis. Protein arginine methyltransferase 1 (Prmt1) is a major enzyme catalyzing asymmetric arginine dimethylation of proteins that are sources of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. Although a potential role of Prmt1 in vascular pathogenesis has been proposed, its role in vascular function has yet to be clarified. Here, we investigated the role and underlying mechanism of Prmt1 in vascular smooth muscle contractility and function. The expression of PRMT1 and contractile-related genes was significantly decreased in the aortas of elderly humans and patients with aortic aneurysms. Mice with VSMC-specific Prmt1 ablation (smKO) exhibited partial lethality, low blood pressure and aortic dilation. The Prmt1-ablated aortas showed aortic dissection with elastic fiber degeneration and cell death. Ex vivo and in vitro analyses indicated that Prmt1 ablation significantly decreased the contractility of the aorta and traction forces of VSMCs. Prmt1 ablation downregulated the expression of contractile genes such as myocardin while upregulating the expression of synthetic genes, thus causing the contractile to synthetic phenotypic switch of VSMCs. In addition, mechanistic studies demonstrated that Prmt1 directly regulates myocardin gene activation by modulating epigenetic histone modifications in the myocardin promoter region. Thus, our study demonstrates that VSMC Prmt1 is essential for vascular homeostasis and that its ablation causes aortic dilation/dissection through impaired myocardin expression.

Research article Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

Lee, Soo-Yeon,Go, Ga-Yeon,Vuong, Tuan Anh,Kim, Jee Won,Lee, Sullim,Jo, Ayoung,An, Jun Min,Kim, Su-Nam,Seo, Dong-Wan,Kim, Jin-Seok,Kim, Yong Kee,Kang, Jong-Sun,Lee, Sang-Jin,Bae, Gyu-Un The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.1

Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing hetero-dimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

Prmt7 Deficiency Causes Reduced Skeletal Muscle Oxidative Metabolism and Age-Related Obesity

Jeong, Hyeon-Ju,Lee, Hye-Jin,Vuong, Tuan Anh,Choi, Kyu-Sil,Choi, Dahee,Koo, Sung-Hoi,Cho, Sung Chun,Cho, Hana,Kang, Jong-Sun American Diabetes Association 2016 Diabetes Vol.65 No.7

<P>Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity. Prmt7(-/-) muscles exhibit decreased oxidative metabolism with decreased expression of genes involved in muscle oxidative metabolism, including PGC-1 alpha. Consistently, Prmt7(-/-) mice exhibited significantly reduced endurance exercise capacities. Furthermore, Prmt7(-/-) mice exhibit decreased energy expenditure, which might contribute to the exacerbated age-related obesity of Prmt7(-/-) mice. Similarly to Prmt7(-/-) muscles, Prmt7 depletion in myoblasts also reduces PGC-1 alpha expression and PGC-1 alpha-promoter driven reporter activities. Prmt7 regulates PGC-1 alpha expression through interaction with and activation of p38 mitogen-activated protein kinase (p38MAPK), which in turn activates ATF2, an upstream transcriptional activator for PGC-1 alpha. Taken together, Prmt7 is a novel regulator for muscle oxidative metabolism via activation of p38MAPK/ATF2/PGC-1 alpha.</P>