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Experimental & Molecular Medicine

Kyoung-Hee Lee, Jinwoo Lee, Jiyeong Jeong, Jisu Woo, Chang-Hoon Lee, Chul-Gyu Yoo
Although inflammation, oxidative stress, and protease-antiprotease imbalance have been referred to as a pathogenic triad in chronic obstructive pulmonary disease (COPD), little is known about how they interact. The objectives of this study were to elucidate the effect of cigarette smoke extract (CSE) on the neutrophil elastase (NE)-induced inflammatory response and its molecular mechanism in bronchial epithelial cells. We observed that NE activated extracellular signal-regulated kinase (ERK) and induced IL-8 production...
July 6, 2018: Experimental & Molecular Medicine
Jing Zhou, Tao Liu, Hao Guo, Hanjin Cui, Pengfei Li, Dandan Feng, En Hu, Qing Huang, Ali Yang, Jun Zhou, Jiekun Luo, Tao Tang, Yang Wang
Lactate accumulation has been observed in the brain with intracerebral hemorrhage (ICH). However, the outcome of lactate accumulation has not been well characterized. Here, we report that lactate accumulation contributes to angiogenesis and neurogenesis in ICH. In the first set of the experiment,  a rat model of ICH was induced by injecting collagenase into the brain. The effects of lactate accumulation on the neurological function, apoptosis, and numbers of newborn endothelial cells and neurons, as well as the proliferation-associated signaling pathway, were evaluated in the rat brain...
July 6, 2018: Experimental & Molecular Medicine
Heung-Woo Park, Woo-Jung Song, Sang-Heon Cho, Michael J McGeachie, Fernando Martinez, Dave Mauger, Bruce G Bender, Kelan G Tantisira
It is well known that depression is associated with asthma symptoms. We assessed the combined effects of genetic factors and depression on asthma symptom severity using Bayesian network (BN) analysis. The common 100 top-ranked single-nucleotide polymorphisms (SNPs) were obtained from two genome-wide association studies of symptom severity in two childhood asthmatics trials (CAMP (Childhood Asthma Management Program) and CARE (Childhood Asthma Research and Education)). Using SNPs plus five discretized variables (depression, anxiety, age, sex, and race), we performed BN analysis in 529 CAMP subjects...
July 4, 2018: Experimental & Molecular Medicine
Eugene Bok, Young Cheul Chung, Ki-Suk Kim, Hyung Hwan Baik, Won-Ho Shin, Byung Kwan Jin
The present study examined the neuroprotective effects of capsaicin (CAP) and explored their underlying mechanisms in a lipopolysaccharide (LPS)-lesioned inflammatory rat model of Parkinson's dieases (PD). LPS was unilaterally injected into the substantia nigra (SN) in the absence or presence of CAP or capsazepine (CZP, a TRPV1 antagonist). The SN tissues were prepared for immunohistochemical staining, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, western blot analysis, blood-brain barrier (BBB) permeability evaluation, and reactive oxygen species (ROS) detection...
July 3, 2018: Experimental & Molecular Medicine
Claudia Dafinger, Markus M Rinschen, Lori Borgal, Carolin Ehrenberg, Sander G Basten, Mareike Franke, Martin Höhne, Manfred Rauh, Heike Göbel, Wilhelm Bloch, F Thomas Wunderlich, Dorien J M Peters, Dirk Tasche, Tripti Mishra, Sandra Habbig, Jörg Dötsch, Roman-Ulrich Müller, Jens C Brüning, Thorsten Persigehl, Rachel H Giles, Thomas Benzing, Bernhard Schermer, Max C Liebau
Ciliopathies comprise a large number of hereditary human diseases and syndromes caused by mutations resulting in dysfunction of either primary or motile cilia. Both types of cilia share a similar architecture. While primary cilia are present on most cell types, expression of motile cilia is limited to specialized tissues utilizing ciliary motility. We characterized protein complexes of ciliopathy proteins and identified the conserved AAA-ATPase Ruvbl1 as a common novel component. Here, we demonstrate that Ruvbl1 is crucial for the development and maintenance of renal tubular epithelium in mice: both constitutive and inducible deletion in tubular epithelial cells result in renal failure with tubular dilatations and fewer ciliated cells...
June 28, 2018: Experimental & Molecular Medicine
Yi-Jing Wang, Pan Zhao, Bing-Dong Sui, Nu Liu, Cheng-Hu Hu, Ji Chen, Chen-Xi Zheng, An-Qi Liu, Kun Xuan, Ya-Ping Pan, Yan Jin
Mesenchymal stem cell (MSC)-based regeneration, specifically cell aggregate or cell sheet engineering, is a promising approach for tissue reconstruction. Considering the advantages of ease of harvest and lack of immune rejection, the application of autologous MSCs (i.e., patients' own MSCs) in regenerative medicine has developed considerable interest. However, the impaired cell viability and regenerative potential following MSCs impacted by disease remain a major challenge. Resveratrol (RSV) exhibits reliable and extensive rejuvenative activities that have received increasing clinical attention...
June 27, 2018: Experimental & Molecular Medicine
Hyun-Young Jang, Jeung-Hyun Koo, Sang-Myeong Lee, Byung-Hyun Park
Previous clinical trials have addressed the beneficial effects of fish oil supplementation on atopic dermatitis. Recently, we reported that fat-1 mice, which can convert n-6 to n-3 polyunsaturated fatty acids (PUFAs), are protected against allergic airway inflammation because their Th2 immune responses are suppressed. Here, we examined the effects of endogenously synthesized n-3 PUFAs on atopic dermatitis, a representative Th2-dominant allergic inflammatory disease. Mouse models of atopic dermatitis-like skin lesions were prepared by epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) or house dust mite (HDM) extract to the ears...
June 13, 2018: Experimental & Molecular Medicine
Fernanda F Cruz, Patricia R M Rocco, Daniel J Weiss
No abstract text is available yet for this article.
June 7, 2018: Experimental & Molecular Medicine
Wookjin Shin, Sang-Kyu Lee, Jeong-Ha Hwang, Jong-Chan Park, Yong-Hee Cho, Eun Ji Ro, Yeonhwa Song, Haeng Ran Seo, Kang-Yell Choi
Although the development of drugs that control Ras is an emerging topic in cancer therapy, no clinically applicable drug is currently available. We have previously utilized knowledge of the Wnt/β-catenin signaling-dependent mechanism of Ras protein stability regulation to identify small molecules that inhibit the proliferation and transformation of various colorectal cancer (CRC) cells via degradation of both β-catenin and Ras. Due to the absence of Ras degradation in cells expressing a nondegradable mutant form of β-catenin and the need to determine an alternative mechanism of Ras degradation, we designed a cell-based system to screen compounds that degrade Ras independent of the Wnt/β-catenin signaling pathway...
June 6, 2018: Experimental & Molecular Medicine
Jun Sub Park, Hyun Lee, Bo Woon Choi, Seonggu Ro, Doyoung Lee, Jeong Eun Na, Jeoung-Ho Hong, Jae-Seon Lee, Bong-Woo Kim, Young-Gyu Ko
Mitsugumin 53 (MG53) is an E3 ligase that induces insulin receptor substrate-1 (IRS-1) ubiquitination and degradation in skeletal muscle. We previously demonstrated that the pharmaceutical disruption of the MG53-IRS-1 interaction improves insulin sensitivity by abrogating IRS-1 ubiquitination and increasing IRS-1 levels in C2C12 myotubes. Here, we developed a novel MG53-IRS-1 interaction disruptor (MID-00935) that ameliorates insulin resistance in diet-induced obese (DIO) mice. MID-00935 disrupted the molecular interaction of MG53 and IRS-1, abrogated MG53-induced IRS-1 ubiquitination and degradation and improved insulin signaling in C2C12 myotubes...
June 6, 2018: Experimental & Molecular Medicine
Yu-Chu Wang, Kung-Chao Chang, Bo-Wen Lin, Jenq-Chang Lee, Chien-Hsien Lai, Li-Jyuan Lin, Yun Yen, Chang-Shen Lin, Shiang-Jie Yang, Peng-Chan Lin, Chung-Ta Lee, Liang-Yi Hung
Heterogeneous nuclear ribonucleoprotein (hnRNP) Q1, an RNA-binding protein, has been implicated in many post-transcriptional processes, including RNA metabolism and mRNA splicing and translation. However, the role of hnRNP Q1 in tumorigenesis remains unclear. We previously performed RNA immunoprecipitation (RIP)-seq analysis to identify hnRNP Q1-interacting mRNAs and found that hnRNP Q1 targets a group of genes that are involved in mitotic regulation, including Aurora-A. Here, we demonstrate that altering the hnRNP Q1 level influences the expression of the Aurora-A protein, but not its mRNA...
June 6, 2018: Experimental & Molecular Medicine
Yue Shen, Matthew R Zeglinski, Christopher T Turner, Sheetal A Raithatha, Zhenguo Wu, Valerio Russo, Cameron Oram, Sho Hiroyasu, Layla Nabai, Hongyan Zhao, Tatjana Bozin, Kathryn Westendorf, Irina Kopko, Rachel Huang, Steve Arns, Jason Tan, Haishan Zeng, Anthony Boey, Richard Liggins, James Jaquith, Dale R Cameron, Anthony Papp, David J Granville
Granzyme B (GzmB) is a serine protease that has long been thought to function exclusively in lymphocyte-mediated apoptosis. In recent years, this paradigm has been revisited due to the recognition that GzmB accumulates in the extracellular milieu in many autoimmune and chronic inflammatory disorders, and contributes to impaired tissue remodeling due to the cleavage of extracellular matrix proteins. Knockout studies suggest that GzmB-mediated cleavage of decorin (DCN) contributes to impaired collagen fibrillogenesis and remodeling...
May 30, 2018: Experimental & Molecular Medicine
Junyeong Jin, Gunwoo Park, Jong Bae Park, Soohyun Kim, Hyori Kim, Junho Chung
Antibody-drug conjugates (ADCs) can selectively deliver cytotoxic agents to tumor cells and are frequently more potent than naked antibodies. However, optimization of the conjugation process between antibodies and cytotoxic agents and characterization of ADCs are laborious and time-consuming processes. Here, we describe a novel ADC platform using a tetravalent bispecific antibody that simultaneously binds to the tumor-associated antigen and a hapten conjugated to a cytotoxic agent. We selected cotinine as the hapten because it is not present in biological systems and is inert and nontoxic...
May 24, 2018: Experimental & Molecular Medicine
Pedro J Esteves, Joana Abrantes, Hanna-Mari Baldauf, Lbachir BenMohamed, Yuxing Chen, Neil Christensen, Javier González-Gallego, Lorenzo Giacani, Jiafen Hu, Gilla Kaplan, Oliver T Keppler, Katherine L Knight, Xiang-Peng Kong, Dennis K Lanning, Jacques Le Pendu, Ana Lemos de Matos, Jia Liu, Shuying Liu, Ana M Lopes, Shan Lu, Sheila Lukehart, Yukari C Manabe, Fabiana Neves, Grant McFadden, Ruimin Pan, Xuwen Peng, Patricia de Sousa-Pereira, Ana Pinheiro, Masmudur Rahman, Natalie Ruvoën-Clouet, Selvakumar Subbian, Maria Jesús Tuñón, Wessel van der Loo, Michael Vaine, Laura E Via, Shixia Wang, Rose Mage
Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases...
May 22, 2018: Experimental & Molecular Medicine
Yin Yang, Qian Li, Qi-Hua He, Ji-Sheng Han, Li Su, You Wan
Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats...
May 21, 2018: Experimental & Molecular Medicine
In-Sook Jeon, Hye-Ryun Kim, Eun-Young Shin, Eung-Gook Kim, Heon-Seok Han, Jin-Tae Hong, Hak-Kyo Lee, Ki-Duk Song, Joong-Kook Choi
Calcium mobilization is necessary for cell movement during embryonic development, lymphocyte synapse formation, wound healing, and cancer cell metastasis. Depletion of calcium in the lumen of the endoplasmic reticulum using inositol triphosphate (IP3) or thapsigargin (TG) is known to induce oligomerization and cytoskeleton-mediated translocation of stromal interaction molecule 1 (STIM1) to the plasma membrane, where it interacts with the calcium release-activated calcium channel Orai1 to mediate calcium influx; this process is referred to as store-operated calcium entry (SOCE)...
May 21, 2018: Experimental & Molecular Medicine
Jin Young Lee, Kyung-Rok Yu, Byung-Chul Lee, Insung Kang, Jae-Jun Kim, Eui-Jung Jung, Hyung-Sik Kim, Yoojin Seo, Soon Won Choi, Kyung-Sun Kang
Defects in the nuclear lamina occur during physiological aging and as. result of premature aging disorders. Aging is also accompanied by an increase in transcription of genes encoding cytokines and chemokines,. phenomenon known as the senescence-associated secretory phenotype (SASP). Progerin and prelamin. trigger premature senescence and loss of function of human mesenchymal stem cells (hMSCs), but little is known about how defects in nuclear lamin. regulate SASP. Here, we show that both progerin overexpression and ZMPSTE24 depletion induce paracrine senescence, especially through the expression of monocyte chemoattractant protein-1 (MCP-1), in hMSCs...
May 14, 2018: Experimental & Molecular Medicine
Hyun-Jung Koh, Ye-Ram Kim, Jae-Sung Kim, Jin-Seung Yun, Sojin Kim, Sun Young Kim, Kiseok Jang, Chul-Su Yang
The tumor suppressor gene CD82/KAI1 is a member of the tetraspanin superfamily and organizes various membrane-based processes. Mycobacterium tuberculosis (MTB) persists in host macrophages by interfering with phagolysosome biogenesis and inflammatory responses, but the role of CD82 in controlling the intracellular survival of pathogenic mycobacteria within macrophages remains poorly understood. In this study, we demonstrated that the virulent MTB strain H37Rv (MTB Rv) induced CD82 promoter hypomethylation, resulting in CD82 expression...
May 14, 2018: Experimental & Molecular Medicine
Ga Young Lee, Seung-Hyun Shin, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA...
May 14, 2018: Experimental & Molecular Medicine
Qian Liu, Bishao Sun, Jiang Zhao, Qingqing Wang, Fan An, Xiaoyan Hu, Zhenxing Yang, Jie Xu, Mingjia Tan, Longkun Li
The Piezo1 channel is a mechanotransduction mediator, and Piezo1 abnormalities have been linked to several clinical disorders. However, the role of the Piezo1 channel in cystitis-associated bladder dysfunction has not been documented. The current study aimed to discover the functional role of this channel in regulating bladder activity during cyclophosphamide (CYP)-induced cystitis. One hundred four female rats were randomly assigned to the control, CYP-4h, CYP-48h and CYP-8d groups. CYP successfully induced acute or chronic cystitis in these rats...
May 7, 2018: Experimental & Molecular Medicine
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