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Takahiko Toyonaga, Minoru Matsuura, Kiyoshi Mori, Yusuke Honzawa, Naoki Minami, Satoshi Yamada, Taku Kobayashi, Toshifumi Hibi, Hiroshi Nakase
Lipocalin 2 (Lcn2), also called neutrophil gelatinase B-associated lipocalin (NGAL), is an anti-microbial peptide originally identified in neutrophil granules. Although Lcn2/NGAL expression is increased in the inflamed intestinal tissues of patients with inflammatory bowel disease, the role of Lcn2/NGAL in the development of intestinal inflammation remains unclear. Here we investigated the role of Lcn2/NGAL in intestinal inflammation using a spontaneous mouse colitis model, interleukin-10 knock out (IL-10 KO) mice...
October 13, 2016: Scientific Reports
Anastasia Asimakopoulou, Sabine Weiskirchen, Ralf Weiskirchen
Lipocalin 2 (LCN2) is a secreted protein that belongs to the Lipocalins, a group of transporters of small lipophilic molecules such as steroids, lipopolysaccharides, iron, and fatty acids in circulation. Two decades after its discovery and after a high variety of published findings, LCN2's altered expression has been assigned to critical roles in several pathological organ conditions, including liver injury and steatosis, renal damage, brain injury, cardiomyopathies, muscle-skeletal disorders, lung infection, and cancer in several organs...
2016: Frontiers in Physiology
Jonas Steenbrugge, Koen Breyne, Sofie Denies, Melissa Dekimpe, Kristel Demeyere, Olivier De Wever, Peter Vermeulen, Steven Van Laere, Niek N Sanders, Evelyne Meyer
Breast tumorigenesis is classically studied in mice by inoculating tumor cells in the fat pad, the adipose compartment of the mammary gland. Alternatively, the mammary ducts, which constitute the luminal mammary gland compartment, also provide a suitable inoculation site to induce breast cancer in murine models. The microenvironments in these compartments influence tumor cell progression, yet this effect has not been investigated in an immunocompetent context. Here, we compared both mammary gland compartments as distinct inoculation sites, taking into account the immunological aspect by inoculating 4T1 tumor cells in immunocompetent mice...
October 6, 2016: Journal of Mammary Gland Biology and Neoplasia
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
September 30, 2016: Purinergic Signalling
Shinji Furuya, Grace A Chappell, Yasuhiro Iwata, Takeki Uehara, Yuki Kato, Hiroshi Kono, Ramon Bataller, Ivan Rusyn
Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl4)-induced fibrosis with chronic intra-gastric alcohol feeding...
November 1, 2016: Toxicology and Applied Pharmacology
Yi Zhong, Anne M Macgregor-Das, Tyler Saunders, Martin Whittle, Alvin Makohon-Moore, Zachary Kohutek, Justin Poling, Brian Herbst, Breanna Javier, Leslie Cope, Steven D Leach, Sunil R Hingorani, Christine A Iacobuzio-Donahue
PURPOSE: TP53 and the TGFβ pathway are major mediators of pancreatic cancer metastasis. The mechanisms by which they cause hematogenous metastasis have not been fully explored. EXPERIMENTAL DESIGN: KPC (LSL-KRASG12D/+;LSL-Trp53R172H/+; Ptf1aCre/+) mice were generated and the frequency and morphology of organ-specific hematogenous metastases compared to that seen in KPTC and KTC littermates (Tgfbr2+/-). Key findings were validated in primary cells from each genotype and samples of human pancreatic cancer liver metastases...
September 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Sandeep Kumar Vashist, John H T Luong
A sensitive and rapid sandwich immunoassay (IA) was developed for human lipocalin-2 (LCN2) by functionalizing a KOH-treated polystyrene microtiter plate with multiwalled carbon nanotubes (MWCNTs) dispersed in 3-aminoproyltriethoxysilane (APTES). The significantly increased surface area due to the presence of MWCNTs led to a high immobilization density of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) activated anti-LCN2 capture antibodies (Ab). The anti-LCN2 Ab-bound MTPs were stable for 6 weeks when stored in 0...
September 3, 2016: Biosensors & Bioelectronics
Guanxiong Ding, Jianqing Wang, Chenchen Feng, Haowen Jiang, Jianfeng Xu, Qiang Ding
BACKGROUND: Castration-resistant prostate cancer (CRPC) is the lethal phenotype of prostate cancer. Lipocalin 2 (LCN2) is aberrantly expressed in many cancers including primary prostate cancer (PCa), but its role in CRPC has not been reported. RESULTS: LCN2 expression was upregulated in human primary PCa and CRPC tissues. Overexpression of LCN2 promoted C4-2B and 22RV1 cell proliferation while knockdown of LCN2 markedly inhibited C4-2B and 22RV1 cell growth. LCN2 overexpression led to increased AR downstream gene SLC45A3 without upregulating AR expression...
September 1, 2016: Oncotarget
Maria Elizabeth de Sousa Rodrigues, Mandakh Bekhbat, Madelyn C Houser, Jianjun Chang, Douglas I Walker, Dean P Jones, Claudia M P Oller do Nascimento, Christopher J Barnum, Malú G Tansey
The mechanisms underlying the association between chronic psychological stress, development of metabolic syndrome (MetS), and behavioral impairment in obesity are poorly understood. The aim of the present study was to assess the effects of mild chronic psychological stress on metabolic, inflammatory, and behavioral profiles in a mouse model of diet-induced obesity. We hypothesized that (1) high-fat high-fructose diet (HFHF) and psychological stress would synergize to mediate the impact of inflammation on the central nervous system in the presence of behavioral dysfunction, and that (2) HFHF and stress interactions would impact insulin and lipid metabolism...
September 1, 2016: Brain, Behavior, and Immunity
Hiroyuki Tsuda, Tomomi Kotani, Tomoko Nakano, Kenji Imai, Shima Hirako, Hua Li, Fumitaka Kikkawa
BACKGROUND: Congenital diaphragmatic hernia (CDH) causes pulmonary hypoplasia, which are often fatal. We established a new biomarker for fetal lung hypoplasia in CDH. METHODS: We collected newborn lung tissue specimens at E21 from normal and nitrofen-induced CDH rats (administered 100mg orally at E9) and performed a microarray analysis and real-time PCR (RT-PCR). Sixty-three human amniotic fluid (AF) samples, including samples from isolated CDH cases (n=33) and Cesarean section (CS) cases without fetal complications (controls) (n=30), were obtained...
November 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
M Xu, Y Zhang, H Cheng, Y Liu, X Zou, N Zhan, S Xiao, Y Xia
Recent studies strongly suggested that transcription factor 7-like 1 (Tcf7l1, also known as Tcf3) is involved in the differentiation of several types of cells, and demonstrated that Tcf7l1 modulates keratinocytes physiologically through regulating lipocalin 2 (LCN2), a key regulator of cell differentiation. To reveal the potential role of Tcf7l1 in the dysregulation of keratinocyte differentiation, both Tcf7l1 and LCN2 were determined in a variety of skin disorders. The in vitro effect of Tcf7l1 on keratinocyte differentiation was studied by culturing SCC-13 cells, and the human foreskin keratinocytes (HFKs) that were transfected with vectors for overexpressing human papillomavirus E6/E7 or Tcf7l1 genes...
2016: Cell Death Discovery
Yanbo Wang, Weikang Qian, Bo Yuan
Smoking is the major cause of lung cancer and the leading cause of cancer-related death in the world. The most current view about lung cancer is no longer limited to individual genes being mutated by any carcinogenic insults from smoking. Instead, tumorigenesis is a phenotype conferred by many systematic and global alterations, leading to extensive heterogeneity and variation for both the genotypes and phenotypes of individual cancer cells. Thus, strategically it is foremost important to develop a methodology to capture any consistent and global alterations presumably shared by most of the cancerous cells for a given population...
August 12, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Kun-Chun Chiang, Chun-Nan Yeh, Cheng-Cheng Huang, Ta-Sen Yeh, Jong-Hwei S Pang, Jun-Te Hsu, Li-Wei Chen, Sheng-Fong Kuo, Atsushi Kittaka, Tai C Chen, Horng-Heng Juang
Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)₂D₃, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)₂D₃, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)₂D₃ has been found in some cancer cells with CYP27B1 expression...
2016: International Journal of Molecular Sciences
Piu Saha, Vishal Singh, Xia Xiao, Beng San Yeoh, Matam Vijay-Kumar
The data herein is related to the research article entitled "Microbiota-inducible innate immune siderophore binding protein Lipocalin 2 is critical for intestinal homeostasis" (Singh et al., 2016) [1]. In the present article, we monitored dextran sodium sulfate (DSS)-induced colitis development upon Lipocalin 2 (Lcn2) neutralization, and examined the survival of Lcn2 deficient (Lcn2KO) mice and their WT littermates upon DSS challenge. To dissect the relative contribution of immune and non-immune cells-derived Lcn2 in mediating protection against gut inflammation, we generated respective bone marrow chimera and evaluated their susceptibility to IL-10 receptor neutralization-induced chronic colitis...
September 2016: Data in Brief
Kyoungho Suk
Lipocalin-2 (LCN2) is a member of the secreted lipocalin protein family. LCN2 is also a representative gliocalin that is primarily released by glial cells, as well as acts upon them. Astrocytes are one of the major cellular sources of LCN2 under brain injury conditions. Astrocytes secrete LCN2 to promote neuroinflammation. Studies using Lcn2 knockout animals and cultured neural cells suggest an important role of LCN2 in regulating the development of hemorrhagic and ischemic stroke as well as other brain injuries...
September 2016: Progress in Neurobiology
Jia-Rong Gao, Xiu-Juan Qin, Hui Jiang, Ting Wang, Jun-Mei Song, Shuang-Zhi Xu
BACKGROUND AND AIM: Chronic glomerulonephritis (CGN) is a primary glomerular disease that is related to immune-mediated inflammatory diseases. Qi Teng Xiao Zhuo granules have been proposed as a prescription of traditional Chinese medicine for treatment of CGN, but the comprehensive molecular mechanism underlying this therapeutic effect is not clear to date. The aim of this study was to evaluate and analyze the possible roles and molecular mechanisms of Qi Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats...
August 3, 2016: Journal of Ethnopharmacology
Akira Kohda, Soh Yamazaki, Hideki Sumimoto
The nuclear protein IκBζ, comprising the N-terminal trans-activation domain and the C-terminal ankyrin repeat (ANK) domain composed of seven ANK motifs, activates transcription of a subset of nuclear factor-κB (NF-κB)-dependent innate immune genes such as Lcn2 encoding the antibacterial protein lipocalin-2. Lcn2 activation requires formation of a complex containing IκBζ and NF-κB p50, a transcription factor that harbors the DNA-binding Rel homology region but lacks a trans-activation domain, on the promoter with the canonical NF-κB-binding site (κB site) and its downstream cytosine-rich element...
September 23, 2016: Journal of Biological Chemistry
W-S Choi, J-S Chun
OBJECTIVE: Lipocalin-2 (LCN2) is a recently characterized adipokine that is upregulated in chondrocytes treated with pro-inflammatory mediators and in the synovial fluid of osteoarthritis (OA) patients. Here, we explored the in vivo functions of LCN2 in OA cartilage destruction in mice. METHODS: The expression levels of LCN2 were determined at the mRNA and protein levels in primary cultured mouse chondrocytes and in human and mouse OA cartilage. Experimental OA was induced in wild-type (WT) or Lcn2-knockout (KO) mice by destabilization of the medial meniscus (DMM) or intra-articular (IA) injection of adenoviruses expressing hypoxia-inducible factor (HIF)-2α (Ad-Epas1), ZIP8 (Ad-Zip8), or LCN2 (Ad-Lcn2)...
July 29, 2016: Osteoarthritis and Cartilage
Yuqi Luo, Xiaojing Ma, Xiaoping Pan, Yiting Xu, Qin Xiong, Yunfeng Xiao, Yuqian Bao, Weiping Jia
Serum lipocalin-2 (LCN2) plays an important role in the regulation of the obesity-associated dysmetabolic state and cardiovascular disease. However, relatively little is known about the relationship between serum LCN2 levels and body fat content and distribution. We examined the associations of total body fat content and abdominal fat distribution with serum LCN2 levels in Chinese men.The study was based on a cross-sectional analysis of data for 1203 Chinese men aged 22 to 78 years from the Shanghai Obesity Study...
July 2016: Medicine (Baltimore)
Kun-Chun Chiang, Shu-Yuan Hsu, Sheng-Jia Lin, Chun-Nan Yeh, Jong-Hwei S Pang, Shang-Yu Wang, Jun-Te Hsu, Ta-Sen Yeh, Li-Wei Chen, Sheng-Fong Kuo, Yi-Chuan Cheng, Horng-Heng Juang
BACKGROUND/AIM: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) insufficiency is commonly found in breast cancer patients with metastasis. We investigated the mechanisms by which PTEN affects breast cancer metastatic behavior. MATERIALS AND METHODS: Migration and invasion assay, western blot, immunofluorescent staining and zebrafish animal model were applied. RESULTS: We showed that PTEN insufficiency induced an increase in MCF-7 cell migration and invasion through induction of epithelial-mesenchymal transition (EMT), which was triggered by up-regulation of the EMT-inducing transcriptional factors Zeb1, Zeb2, Snail, Slug and Twist...
August 2016: Anticancer Research
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