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Experimental & Molecular Medicine

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https://www.readbyqxmd.com/read/29789565/the-wide-utility-of-rabbits-as-models-of-human-diseases
#1
REVIEW
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
https://www.readbyqxmd.com/read/29780163/heteromerization-of-%C3%AE-opioid-receptor-and-cholecystokinin-b-receptor-through-the-third-transmembrane-domain-of-the-%C3%AE-opioid-receptor-contributes-to-the-anti-opioid-effects-of-cholecystokinin-octapeptide
#2
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
https://www.readbyqxmd.com/read/29780159/modulation-of-store-operated-calcium-entry-and-nascent-adhesion-by-p21-activated-kinase-1
#3
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
https://www.readbyqxmd.com/read/29760459/gata4-dependent-regulation-of-the-secretory-phenotype-via-mcp-1-underlies-lamin-a-mediated-human-mesenchymal-stem-cell-aging
#4
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
https://www.readbyqxmd.com/read/29760437/cd82-hypomethylation-is-essential-for-tuberculosis-pathogenesis-via-regulation-of-runx1-rab5-22
#5
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
https://www.readbyqxmd.com/read/29760417/ndrg3-lowers-the-metastatic-potential-in-prostate-cancer-as-a-feedback-controller-of-hypoxia-inducible-factors
#6
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
https://www.readbyqxmd.com/read/29735991/increased-piezo1-channel-activity-in-interstitial-cajal-like-cells-induces-bladder-hyperactivity-by-functionally-interacting-with-ncx1-in-rats-with-cyclophosphamide-induced-cystitis
#7
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
https://www.readbyqxmd.com/read/29717122/therapeutic-potential-of-a-phospholipase-d1-inhibitory-peptide-fused-with-a-cell-penetrating-peptide-as-a-novel-anti-asthmatic-drug-in-a-der-f-2-induced-airway-inflammation-model
#8
Yun Young Lee, So Young Lee, Shin-Young Park, Hye-Jin Choi, Eung-Gook Kim, Joong-Soo Han
Asthma is a chronic lung disease that causes airflow obstruction due to airway inflammation. However, its therapeutics remain inadequate. We previously reported that phospholipase D1 (PLD1) is a key enzyme involved in the production of pro-inflammatory cytokines in airway inflammation induced by the house dust mite allergen Dermatophagoides farinae 2 (Der f 2). We also revealed that PLD1 is specifically inactivated by AP180 (assembly protein, 180 kDa) and identified the PLD1-specific binding motif (TVTSP) of AP180...
May 1, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29717112/gastrin-stimulates-pancreatic-cancer-cell-directional-migration-by-activating-the-g%C3%AE-12-13-rhoa-rock-signaling-pathway
#9
Ganggang Mu, Qianshan Ding, Hongyan Li, Li Zhang, Lingli Zhang, Ke He, Lu Wu, Yunchao Deng, Dongmei Yang, Lianlian Wu, Ming Xu, Jie Zhou, Honggang Yu
The mechanism by which gastrin promotes pancreatic cancer cell metastasis is unclear. The process of directing polarized cancer cells toward the extracellular matrix is principally required for invasion and distant metastasis; however, whether gastrin can induce this process and its underlying mechanism remain to be elucidated. In this study, we found that gastrin-induced phosphorylation of paxillin at tyrosine 31/118 and RhoA activation as well as promoted the metastasis of PANC-1 cancer cells. Depletion of Gα12 and Gα13 inhibited the phosphorylation of paxillin and downstream activation of GTP-RhoA, blocked the formation and aggregation of focal adhesions and facilitated polarization of actin filaments induced by gastrin...
May 1, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29717107/exendin-4-ameliorates-high-glucose-induced-fibrosis-by-inhibiting-the-secretion-of-mir-192-from-injured-renal-tubular-epithelial-cells
#10
Yijie Jia, Zongji Zheng, Meiping Guan, Qian Zhang, Yang Li, Ling Wang, Yaoming Xue
Extracellular vesicles (EVs), which contain microRNA (miRNA), constitute a novel means of cell communication that may contribute to the inevitable expansion of renal fibrosis during diabetic kidney disease (DKD). Exendin-4 is effective for treating DKD through its action on GLP1R. However, the effect of exendin-4 on EV miRNA expression and renal cell communication during the development of DKD remains unknown. In this study, we found that EVs derived from HK-2 cells pre-treated with exendin-4 and high glucose (Ex-HG), which were taken up by normal HK-2 cells, resulted in decreased levels of FN and Col-I compared with EVs from HK-2 cells pre-treated with HG alone...
May 1, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29717106/role-of-clusterin-progranulin-in-toluene-diisocyanate-induced-occupational-asthma
#11
Gil-Soon Choi, Hoang Kim Tu Trinh, Eun-Mi Yang, Young-Min Ye, Yoo Seob Shin, Seung-Hyun Kim, Hae-Sim Park
Toluene diisocyanate (TDI) exposure induces oxidative stress and epithelial cell-derived inflammation, which affect the pathogenesis of TDI-induced occupational asthma (TDI-OA). Recent studies suggested a role for clusterin (CLU) and progranulin (PGRN) in oxidative stress-mediated airway inflammation. To evaluate CLU and PGRN involvement in airway inflammation in TDI-OA, we measured their serum levels in patients with TDI-OA, asymptomatic exposed controls (AECs), and unexposed healthy normal controls (NCs)...
May 1, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29717105/long-noncoding-rna-dancr-promotes-colorectal-cancer-proliferation-and-metastasis-via-mir-577-sponging
#12
Yong Wang, Zhi Lu, Ningnin Wang, Jianzhou Feng, Junjie Zhang, Lan Luan, Wei Zhao, Xiandong Zeng
Long non-coding RNAs (lncRNAs) play key roles in various malignant tumors, including colorectal cancer (CRC). Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is overexpressed in CRC patients, but whether it affects CRC proliferation and metastasis via regulation of heat shock protein 27 (HSP27) remains unclear. In the present study, we found that DANCR was highly expressed and correlated with proliferation and metastasis in CRC. In addition, we demonstrated that DANCR and HSP27 were both targets of microRNA-577 (miR-577) and shared the same binding site...
May 1, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700355/claudin-11-regulates-bone-homeostasis-via-bidirectional-ephb4-ephrinb2-signaling
#13
Jong Min Baek, Yoon-Hee Cheon, Sung Chul Kwak, Hong Young Jun, Kwon-Ha Yoon, Myeung Su Lee, Ju-Young Kim
Claudins (Cldns) are well-established components of tight junctions (TJs) that play a pivotal role in the modulation of paracellular permeability. Several studies have explored the physiologic aspects of Cldn family members in bone metabolism. However, the effect of Cldn11, a major component of central nervous system myelin, on bone homeostasis has not been reported. In this study, we demonstrate that Cldn11 is a potential target for bone disease therapeutics as a dual modulator of osteogenesis enhancement and osteoclastogenesis inhibition...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700292/enhancement-of-5-ht-2a-receptor-function-and-blockade-of-kv1-5-by-mk801-and-ketamine-implications-for-pcp-derivative-induced-disease-models
#14
Haiyue Lin, Jae Gon Kim, Sang Woong Park, Hyun Ju Noh, Jeong Min Kim, Chang Yong Yoon, Nam-Sik Woo, Bokyung Kim, Sung Il Cho, Bok Hee Choi, Dong Jun Sung, Young Min Bae
MK801 and ketamine, which are phencyclidine (PCP) derivative N-methyl-d-aspartate receptor (NMDAr) blockers, reportedly enhance the function of 5-hydroxytryptamine (HT)-2A receptors (5-HT2A Rs). Both are believed to directly affect the pathogenesis of schizophrenia, as well as hypertension. 5-HT2A R signaling involves the inhibition of Kv conductance. This study investigated the interaction of these drugs with Kv1.5, which plays important roles in 5-HT2A R signaling and in regulating the excitability of the cardiovascular and nervous system, and the potential role of this interaction in the enhancement of the 5-HT2A R-mediated response...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700291/protectin-dx-increases-alveolar-fluid-clearance-in-rats-with-lipopolysaccharide-induced-acute-lung-injury
#15
Xiao-Jun Zhuo, Yu Hao, Fei Cao, Song-Fan Yan, Hui Li, Qian Wang, Bi-Huan Cheng, Bin-Yu Ying, Fang Gao Smith, Sheng-Wei Jin
Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/kg) administration, and alveolar fluid clearance was measured in live rats (n = 8). In primary rat ATII epithelial cells, protectin DX (3.605 × 10-3  mg/l) was added to the culture medium with LPS for 6 h...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700289/rcp-induces-fak-phosphorylation-and-ovarian-cancer-cell-invasion-with-inhibition-by-curcumin
#16
So Ra Choe, Yu Na Kim, Chang Gyo Park, Kyung Hwa Cho, Do Yeun Cho, Hoi Young Lee
Rab coupling protein (RCP) aggravates cancer cell metastasis and has been implicated in various cancer patient outcomes. Recently, we showed that RCP induces Slug expression and cancer cell invasion by stabilizing the β1 integrin protein. In the present study, we demonstrated that FAK is implicated in RCP-induced EGFR phosphorylation and ovarian cancer cell invasion with inhibition by curcumin. Ectopic expression of RCP induced FAK phosphorylation, which links β1 integrin with EGFR and participates in a positive regulation loop with EGFR...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700288/atp-depletion-during-mitotic-arrest-induces-mitotic-slippage-and-apc-c-cdh1-dependent-cyclin-b1-degradation
#17
Yun Yeon Park, Ju-Hyun Ahn, Min-Guk Cho, Jae-Ho Lee
ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700287/mir-125a-5p-ameliorates-monocrotaline-induced-pulmonary-arterial-hypertension-by-targeting-the-tgf-%C3%AE-1-and-il-6-stat3-signaling-pathways
#18
Zongye Cai, Jian Li, Qi Zhuang, Xueming Zhang, Ancai Yuan, Lan Shen, Kang Kang, Bo Qu, Yuanjia Tang, Jun Pu, Deming Gou, Jieyan Shen
Pulmonary vascular remodeling due to excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) is the hallmark feature of pulmonary arterial hypertension (PAH). Recent evidence suggests that miR-125a-5p plays a role in a rat model of monocrotaline-induced PAH (MCT-PAH); however, the underlying mechanism is currently unknown. Here, we examined the expression profile of miR-125a-5p in MCT-PAH rats and investigated the putative therapeutic effect of miR-125a-5p using the miR-125a-5p agomir...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700284/mutation-of-ipo13-causes-recessive-ocular-coloboma-microphthalmia-and-cataract
#19
Xiu-Feng Huang, Lue Xiang, Wan Cheng, Fei-Fei Cheng, Kai-Wen He, Bo-Wen Zhang, Si-Si Zheng, Ru-Yi Han, Yi-Han Zheng, Xiao-Tao Xu, Huan-Yun Yu, Wenjuan Zhuang, Yuk Fai Leung, Zi-Bing Jin
Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p.R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29700280/altered-akap12-expression-in-portal-fibroblasts-and-liver-sinusoids-mediates-transition-from-hepatic-fibrogenesis-to-fibrosis-resolution
#20
Hye Shin Lee, Jinhyeok Choi, Taekwon Son, Hee-Jun Wee, Sung-Jin Bae, Ji Hae Seo, Ji Hyun Park, Soo Hyung Ryu, Danbi Lee, Myoung Kuk Jang, Eunsil Yu, Young-Hwa Chung, Kyu-Won Kim
Liver fibrosis can be reversed by removing its causative injuries; however, the molecular mechanisms mediating the resolution of liver fibrogenesis are poorly understood. We investigate the role of a scaffold protein, A-Kinase Anchoring Protein 12 (AKAP12), during liver fibrosis onset, and resolution. Biliary fibrogenesis and fibrosis resolution was induced in wild-type (WT) or AKAP12-deficient C57BL/6 mice through different feeding regimens with 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing chow...
April 27, 2018: Experimental & Molecular Medicine
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