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Experimental & Molecular Medicine

You-Sun Kim, Goohyeon Hong, Doh Hyung Kim, Young Min Kim, Yoon-Keun Kim, Yeon-Mok Oh, Young-Koo Jee
Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice...
November 14, 2018: Experimental & Molecular Medicine
Insung Kang, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Eun-Ah Sung, Seung Eun Lee, Nari Shin, Soon Won Choi, Yoojin Seo, Hyung-Sik Kim, Kyung-Sun Kang
We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite...
November 14, 2018: Experimental & Molecular Medicine
Wen-Ling Dai, Xin-Tong Liu, Yi-Ni Bao, Bing Yan, Nan Jiang, Bo-Yang Yu, Ji-Hua Liu
Morphine tolerance remains a challenge in the management of chronic pain in the clinic. As shown in our previous study, the dopamine D2 receptor (D2DR) expressed in spinal cord neurons might be involved in morphine tolerance, but the underlying mechanisms remain to be elucidated. In the present study, selective spinal D2DR blockade attenuated morphine tolerance in mice by inhibiting phosphatidylinositol 3 kinase (PI3K)/serine-threonine kinase (Akt)-mitogen activated protein kinase (MAPK) signaling in a μ opioid receptor (MOR)-dependent manner...
November 14, 2018: Experimental & Molecular Medicine
Gena Lee, Yun Seong Jeong, Do Won Kim, Min Jun Kwak, Jiwon Koh, Eun Wook Joo, Ju-Seog Lee, Susie Kah, Yeong-Eun Sim, Sun Young Yim
Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941)...
November 14, 2018: Experimental & Molecular Medicine
Jianle Wang, Majid Nisar, Chongan Huang, Xiangxiang Pan, Dongdong Lin, Gang Zheng, Haiming Jin, Deheng Chen, Naifeng Tian, Qianyu Huang, Yue Duan, Yingzhao Yan, Ke Wang, Congcong Wu, Jianing Hu, Xiaolei Zhang, Xiangyang Wang
Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress. We subsequently activated SIRT3 using honokiol to evaluate its therapeutic potential for IVDD...
November 12, 2018: Experimental & Molecular Medicine
Jae Hyouk Choi, Oleg Yarishkin, Eunju Kim, Yeonju Bae, Ajung Kim, Seung-Chan Kim, Kanghyun Ryoo, Chang-Hoon Cho, Eun Mi Hwang, Jae-Yong Park
Two-pore domain K+ (K2P) channels have been shown to modulate neuronal excitability. The physiological role of TWIK-1, the first identified K2P channel, in neuronal cells is largely unknown, and we reported previously that TWIK-1 contributes to the intrinsic excitability of dentate gyrus granule cells (DGGCs) in mice. In the present study, we investigated the coexpression of TWIK-1 and TASK-3, another K2P member, in DGGCs. Immunohistochemical staining data showed that TASK-3 proteins were highly localized in the proximal dendrites and soma of DGGCs, and this localization is similar to the expression pattern of TWIK-1...
November 12, 2018: Experimental & Molecular Medicine
Shuhui Zheng, Hang Zhou, Bo Gao, Yongyong Li, Zhiheng Liao, Taifeng Zhou, Chengjie Lian, Zizhao Wu, Deying Su, Tingting Wang, Peiqiang Su, Caixia Xu
This study aimed to verify the effects of estrogen on the onset and development of adolescent idiopathic scoliosis and the mechanisms associated with these effects by constructing a pubescent bipedal rat model. Experiments were conducted to investigate whether scoliosis progression was prevented by a Triptorelin treatment. One hundred twenty bipedal rats were divided into female, OVX (ovariectomy), OVX + E2, Triptorelin, sham, and male groups. According to a spinal radiographic analysis, the scoliosis rates and curve severity of the female and OVX + E2 groups were higher than those in the OVX, Triptorelin, and male groups...
November 7, 2018: Experimental & Molecular Medicine
Soo Yeon Lim, Dong Im Cho, Hye-Yun Jeong, Hye-Jin Kang, Mi Ra Kim, Meeyoung Cho, Yong Sook Kim, Youngkeun Ahn
Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs...
November 5, 2018: Experimental & Molecular Medicine
Mi Nam Lee, Hee-Su Hwang, Sin-Hye Oh, Amir Roshanzadeh, Jung-Woo Kim, Ju Han Song, Eung-Sam Kim, Jeong-Tae Koh
Supplementation of mesenchymal stem cells (MSCs) at sites of bone resorption is required for bone homeostasis because of the non-proliferation and short lifespan properties of the osteoblasts. Calcium ions (Ca2+ ) are released from the bone surfaces during osteoclast-mediated bone resorption. However, how elevated extracellular Ca2+ concentrations would alter MSCs behavior in the proximal sites of bone resorption is largely unknown. In this study, we investigated the effect of extracellular Ca2+ on MSCs phenotype depending on Ca2+ concentrations...
November 5, 2018: Experimental & Molecular Medicine
Mi-Ock Baek, Hae-In Song, Joong-Soo Han, Mee-Sup Yoon
Human endometrium decidualization, a differentiation process involving biochemical and morphological changes, is a prerequisite for embryo implantation and successful pregnancy. Here, we show that the mammalian target of rapamycin (mTOR) is a crucial regulator of 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP)-induced decidualization in human endometrial stromal cells. The level of mSin1 in mTOR complex 2 (mTORC2) and DEPTOR in mTOR complex 1 (mTORC1) decreases during 8-Br-cAMP-induced decidualization, resulting in decreased mTORC2 activity and increased mTORC1 activity...
October 30, 2018: Experimental & Molecular Medicine
Yun-Qiang Wan, Jian-Guo Feng, Mao Li, Mao-Zhou Wang, Li Liu, Xueru Liu, Xiao-Xia Duan, Chun-Xiang Zhang, Xiao-Bin Wang
Ketamine has a rapid, obvious, and persistent antidepressant effect, but its underlying molecular mechanisms remain unknown. Recently, microRNAs (miRNAs) have emerged as important modulators of ketamine's antidepressant effect. We investigated the alteration in miR-29b-3p in the brain of rats subjected to ketamine administration and chronic unpredictable mild stress (CUMS), and a sucrose preference test and forced swimming test were used to evaluate the rats' depressive-like state. We used recombination adeno-associated virus (rAAV) or lentivirus-expressing miR-29b-3p to observe the change in metabotropic glutamate receptor 4 (GRM4)...
October 29, 2018: Experimental & Molecular Medicine
Yvonne Nitschke, Yan Yan, Insa Buers, Kristina Kintziger, Kim Askew, Frank Rutsch
Generalized arterial calcification of infancy (GACI) is associated with widespread arterial calcification and stenoses and is caused by mutations in ENPP1. ENPP1 encodes for ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which cleaves ATP to generate inorganic pyrophosphate (PPi ) and adenosine monophosphate (AMP) extracellularly. The current study was designed to define the prevalence of arterial stenoses in GACI individuals and to identify the mechanism through which ENPP1 deficiency causes intimal proliferation...
October 29, 2018: Experimental & Molecular Medicine
Jin-Kwan Lee, Geun-Hyoung Ha, Hyun-Soo Kim, Chang-Woo Lee
The brain-expressed X-linked 4 (BEX4) gene has been recently identified as a mediator of microtubule hyperacetylation through sirtuin 2 inhibition and is highly overexpressed in human cancers. However, the gain-of-function molecular mechanism of the BEX4 gene in human cancers still needs to be elucidated. This study shows that BEX4 colocalizes and interacts with Polo-like kinase 1 (PLK1) at centrosomes, spindle poles, and midbodies, particularly during mitosis. Interestingly, PLK1-mediated phosphorylation upregulates the stability of BEX4 protein, and the PLK1-BEX4 interaction allows abnormal mitotic cells to adapt to aneuploidy rather than undergo apoptotic cell death...
October 22, 2018: Experimental & Molecular Medicine
Hee Yeon Kim, Dong Keon Kim, Seung-Hyun Bae, HyeRan Gwak, Ji Hoon Jeon, Jong Kwang Kim, Byung Il Lee, Hye Jin You, Dong Hoon Shin, Young-Ho Kim, Soo Youl Kim, Sung-Sik Han, Jin-Kyoung Shim, Ji-Hyun Lee, Seok-Gu Kang, Hyonchol Jang
Glioblastoma is a highly malignant tumor that easily acquires resistance to treatment. The stem-cell-like character (stemness) has been thought to be closely associated with the treatment resistance of glioblastoma cells. In this study, we determined that farnesyl diphosphate synthase (FDPS), a key enzyme in isoprenoid biosynthesis, plays an important role in maintaining glioblastoma stemness. A comparison of the mRNA expression in patient-derived glioblastoma sphere cells, which maintain stemness, and their differentiated counterparts, which lose stemness, via RNA sequencing showed that most of the altered genes were networked in the cholesterol biosynthesis pathway...
October 17, 2018: Experimental & Molecular Medicine
Eun Kyung Choi, Jeong-A Lim, Jong Kwang Kim, Moon Sun Jang, Sun Eui Kim, Hye Jung Baek, Eun Jung Park, Tae Hyun Kim, Chu-Xia Deng, Rui-Hong Wang, Sang Soo Kim
Germline BRCA1 mutations predispose women to breast and ovarian cancer. BRCA1, a large protein with multiple functional domains, interacts with numerous proteins involved in many important biological processes and pathways. However, to date, the role of BRCA1 interactions at specific stages in the progression of mammary tumors, particularly in relation to cell cycle regulation, remains elusive. Here, we demonstrate that BRCA1 interacts with cyclin B1, a crucial cell cycle regulator, and that their interaction is modulated by DNA damage and cell cycle phase...
October 16, 2018: Experimental & Molecular Medicine
Jae Min Lee, Sun Sil Choi, Yo Han Lee, Keon Woo Khim, Sora Yoon, Byung-Gyu Kim, Dougu Nam, Pann-Ghill Suh, Kyungjae Myung, Jang Hyun Choi
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that regulates adipocyte differentiation and glucose homeostasis. The transcriptional activity of PPARγ is regulated not only by ligands but also by post-translational modifications (PTMs). In this study, we demonstrate that a novel E3 ligase of PPARγ, tripartite motif-containing 25 (TRIM25), directly induced the ubiquitination of PPARγ, leading to its proteasome-dependent degradation. During adipocyte differentiation, both TRIM25 mRNA and protein expression significantly decreased and negatively correlated with the expression of PPARγ...
October 15, 2018: Experimental & Molecular Medicine
Carolina Méndez-Blanco, Flavia Fondevila, Andrés García-Palomo, Javier González-Gallego, José L Mauriz
Sorafenib, a multikinase inhibitor with antiproliferative, antiangiogenic, and proapoptotic properties, constitutes the only effective first-line drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Despite its capacity to increase survival in HCC patients, its success is quite low in the long term owing to the development of resistant cells through several mechanisms. Among these mechanisms, the antiangiogenic effects of sustained sorafenib treatment induce a reduction of microvessel density, promoting intratumoral hypoxia and hypoxia-inducible factors (HIFs)-mediated cellular responses that favor the selection of resistant cells adapted to the hypoxic microenvironment...
October 12, 2018: Experimental & Molecular Medicine
Jihye Ahn, Jin Gyeong Lee, Chuevin Chin, Suna In, Aerin Yang, Hee-Sung Park, Jaehoon Kim, Jeong Hyeon Park
Mitogen- and stress-activated kinase 1 (MSK1) is a chromatin kinase that facilitates activator-dependent transcription by altering chromatin structure through histone H3 phosphorylation. The kinase activity of MSK1 is activated by intramolecular autophosphorylation, which is initially triggered by the activation of upstream mitogen-activated protein kinases (MAPKs), such as p38 and ERK1/2. MSK1 has been implicated in the expression of p21, a p53 target gene; however, the precise connection between MSK1 and p53 has not been clearly elucidated...
October 10, 2018: Experimental & Molecular Medicine
Gerrit Wolters-Eisfeld, Baris Mercanoglu, Bianca T Hofmann, Thomas Wolpers, Claudia Schnabel, Sönke Harder, Pascal Steffen, Kai Bachmann, Babett Steglich, Jörg Schrader, Nicola Gagliani, Hartmut Schlüter, Cenap Güngör, Jakob R Izbicki, Christoph Wagener, Maximilian Bockhorn
Cosmc is ubiquitously expressed and acts as a specific molecular chaperone assisting the folding and stability of core 1 synthase. Thus, it plays a crucial role in the biosynthesis of O-linked glycosylation of proteins. Here, we show that ablation of Cosmc in the exocrine pancreas of mice causes expression of truncated O-glycans (Tn antigen), resulting in exocrine pancreatic insufficiency with decreased activities of digestive enzymes and diabetes. To understand the molecular causes of the pleiotropic phenotype, we used Vicia villosa agglutinin to enrich Tn antigen-modified proteins from Cosmc-KO pancreatic lysates and performed a proteomic analysis...
October 10, 2018: Experimental & Molecular Medicine
Giulia Anzalone, Giusy Daniela Albano, Angela Marina Montalbano, Loredana Riccobono, Anna Bonanno, Rosalia Gagliardo, Fabio Bucchieri, Roberto Marchese, Monica Moscato, Mirella Profita
Thymic stromal lymphopoietin (TSLP) is a cytokine expressed in the epithelium, involved in the pathogenesis of chronic disease. IL-17A regulates airway inflammation, oxidative stress, and reduction of steroid sensitivity in chronic obstructive pulmonary disease (COPD). TSLP and IL-17A were measured in induced sputum supernatants (ISs) from healthy controls (HC), healthy smokers (HS), and COPD patients by enzyme-linked immunosorbent assay. Human bronchial epithelial cell line (16HBE) and normal bronchial epithelial cells were stimulated with rhIL-17A or ISs from COPD patients to evaluate TSLP protein and mRNA expression...
October 5, 2018: Experimental & Molecular Medicine
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