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Akinori Okumura, Hiroyuki Unoki-Kubota, Natsuyo Yoshida-Hata, Ritsuko Yamamoto-Honda, Shigeo Yamashita, Minoru Iwata, Kazuyuki Tobe, Hiroshi Kajio, Mitsuhiko Noda, Naomichi Katai, Satoshi Yamagoe, Yasushi Kaburagi
BACKGROUND: Vascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR. METHODS: The study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR...
October 28, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently we have shown that co-expression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to HCC in mice that represents around 10% of human HCC. In the current study, we investigate if Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Akinori Okumura, Hiroyuki Unoki-Kubota, Natsuyo Yoshida-Hata, Ritsuko Yamamoto-Honda, Shigeo Yamashita, Minoru Iwata, Kazuyuki Tobe, Hiroshi Kajio, Mitsuhiko Noda, Naomichi Katai, Satoshi Yamagoe, Yasushi Kaburagi
BACKGROUND: Vascular endothelial growth factor (VEGF) signaling is an important pathway in the development of diabetic retinopathy (DR). A recent report showed that leukocyte cell-derived chemotaxin 2 (LECT2) suppresses the VEGF signaling in endothelial cells. However, the clinical relevance of LECT2 in DR is unknown. This study aimed to investigate serum LECT2 levels and the presence of DR. METHODS: The study included 230 people with type 2 diabetes mellitus (DM), 95 with DR and 135 without DR...
December 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
H X Shen, L Li, Q Chen, Y Q He, C H Yu, C Q Chu, X J Lu, J Chen
Helicobacter pylori employs unique methods to colonize the stomach, which induces chronic inflammation. It is also able to avoid eradication by macrophages and other immune cells. Leukocyte cell-derived chemotaxin 2 (LECT2), a multi-functional cytokine involved in many pathological conditions, has recently been shown to activate macrophages via the CD209a receptor. Therefore, we aimed to investigate the effects of LECT2 on H. pylori-infected macrophages. Macrophages were treated with recombinant LECT2, and both their ability to kill H...
October 24, 2016: Genetics and Molecular Research: GMR
Wei Zou, Ao Shen, Xintong Dong, Madina Tugizova, Yang K Xiang, Kang Shen
Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells...
October 5, 2016: ELife
Xin-Jiang Lu, Qiang Chen, Ye-Jing Rong, Guan-Jun Yang, Chang-Hong Li, Ning-Yi Xu, Chao-Hui Yu, Hui-Ying Wang, Shun Zhang, Yu-Hong Shi, Jiong Chen
Haematopoietic stem cells (HSCs) can differentiate into cells of all lineages in the blood. However, the mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. Here we show that leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional cytokine, induces HSC expansion and mobilization. Recombinant LECT2 administration results in HSC expansion in the bone marrow and mobilization to the blood via CD209a. The effect of LECT2 on HSCs is reduced after specific depletion of macrophages or reduction of osteolineage cells...
2016: Nature Communications
Keita Chikamoto, Hirofumi Misu, Hiroaki Takayama, Akihiro Kikuchi, Kiyo-Aki Ishii, Fei Lan, Noboru Takata, Natsumi Tajima-Shirasaki, Yumie Takeshita, Hirohiko Tsugane, Shuichi Kaneko, Seiichi Matsugo, Toshinari Takamura
Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days...
September 23, 2016: Biochemical and Biophysical Research Communications
Chi-Kuan Chen, Wen-Hsuan Yu, Tsu-Yao Cheng, Min-Wei Chen, Chia-Yi Su, Yi-Chieh Yang, Tsang-Chih Kuo, Ming-Tsan Lin, Ya-Chi Huang, Michael Hsiao, Kuo-Tai Hua, Mien-Chie Hung, Min-Liang Kuo
Hepatocellular carcinoma (HCC) relies on angiogenesis for growth and metastasis. Leukocyte cell-derived chemotaxin 2 (LECT2) is a cytokine and preferentially expressed in the liver. Previous studies have found that LECT2 targets to both immune and tumor cells to suppress HCC development and vascular invasion. Although LECT2 did not affect HCC cells growth in vitro, it still suppressed HCC xenografts growth in immune-deficient mice, suggesting other cells such as stroma cells may also be targeted by LECT2. Here, we sought to determine the role of LECT2 in tumor angiogenesis in HCC patients...
2016: Scientific Reports
Carlos A Díaz-Balzac, Maisha Rahman, María I Lázaro-Peña, Lourdes A Martin Hernandez, Yehuda Salzberg, Cristina Aguirre-Chen, Zaven Kaprielian, Hannes E Bülow
Sensory dendrite arbors are patterned through cell-autonomously and non-cell-autonomously functioning factors [1-3]. Yet, only a few non-cell-autonomously acting proteins have been identified, including semaphorins [4, 5], brain-derived neurotrophic factors (BDNFs) [6], UNC-6/Netrin [7], and the conserved MNR-1/Menorin-SAX-7/L1CAM cell adhesion complex [8, 9]. This complex acts from the skin to pattern the stereotypic dendritic arbors of PVD and FLP somatosensory neurons in Caenorhabditis elegans through the leucine-rich transmembrane receptor DMA-1/LRR-TM expressed on PVD neurons [8, 9]...
September 12, 2016: Current Biology: CB
Kumpei Tanisawa, Hirokazu Taniguchi, Xiaomin Sun, Tomoko Ito, Ryoko Kawakami, Shizuo Sakamoto, Mitsuru Higuchi
No abstract text is available yet for this article.
May 2016: Medicine and Science in Sports and Exercise
Hai Zheng, Takuya Miyakawa, Yoriko Sawano, Atsuko Asano, Akinori Okumura, Satoshi Yamagoe, Masaru Tanokura
Human leukocyte cell-derived chemotaxin 2 (LECT2), which is predominantly expressed in the liver, is a multifunctional protein. LECT2 is becoming a potential therapeutic target for several diseases of worldwide concern such as rheumatoid arthritis, hepatocellular carcinoma, and obesity. Here, we present the crystal structure of LECT2, the first mammalian protein whose structure contains an M23 metalloendopeptidase fold. The LECT2 structure adopts a conserved Zn(II) coordination configuration but lacks a proposed catalytic histidine residue, and its potential substrate-binding groove is blocked in the vicinity of the Zn(II)-binding site by an additional intrachain loop at the N terminus...
August 12, 2016: Journal of Biological Chemistry
Dariusz M Lebensztejn, Marta Flisiak-Jackiewicz, Irena Białokoz-Kalinowska, Anna Bobrus-Chociej, Irina Kowalska
Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities...
2016: Acta Biochimica Polonica
Hirohisa Okabe, Hiroki Kinoshita, Katsunori Imai, Shigeki Nakagawa, Takaaki Higashi, Kota Arima, Hideaki Uchiyama, Toru Ikegami, Norifumi Harimoto, Shinji Itoh, Takatoshi Ishiko, Tomoharu Yoshizumi, Toru Beppu, Satdarshan P S Monga, Hideo Baba, Yoshihiko Maehara
AIM: β-catenin signaling is a major oncogenic pathway in hepatocellular carcinoma (HCC). Since β-catenin phosphorylation by glycogen synthase kinase 3β (GSK3β) and casein kinase 1ε (CK1ε) results in its degradation, mutations affecting these phosphorylation sites cause β-catenin stabilization. However, the relevance of missense mutations in non-phosphorylation sites in exon 3 remains unclear. The current study explores significance of such mutations in addition to addressing the clinical and biological implications of β-catenin activation in human HCC...
2016: PloS One
Tae Woo Jung, Hye Jin Yoo, Kyung Mook Choi
The liver is a central regulator of systemic energy homeostasis and has a pivotal role in glucose and lipid metabolism. Impaired gluconeogenesis and dyslipidemia are often observed in patients with nonalcoholic fatty liver disease (NAFLD). The liver is now recognized to be an endocrine organ that secretes hepatokines, which are proteins that regulate systemic metabolism and energy homeostasis. Hepatokines are known to contribute to the pathogenesis of metabolic syndrome, NAFLD, type 2 diabetes (T2DM), and cardiovascular diseases (CVDs)...
June 2016: BBA Clinical
Christopher P Larsen, Marjorie L Beggs, Jon D Wilson, Sarah L Lathrop
Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition...
June 2016: Amyloid: the International Journal of Experimental and Clinical Investigation
Hai-Ling Ma, Yu-Hong Shi, Xue-Heng Zhang, Ming-Yun Li, Jiong Chen
Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine involved in many diseases in which immune dysfunction is present. Ayu LECT2 (PaLECT2), which interacts with a C-type lectin receptor (PaCLR), was shown to activate ayu head kidney-derived monocytes/macrophages (MO/MΦ) to improve the outcomes of fish upon bacterial infections. However, it is not known if PaCLR mediates PaLECT2 effects on ayu MO/MΦ. In this study, we determined the role of PaCLR in signal transduction of PaLECT2 on ayu MO/MΦ...
April 2016: Fish & Shellfish Immunology
Guoli Yang, Wen Fang, Tie Liu, Fuming He, Xuepeng Chen, Yi Zhou, Xiaoxu Guan
OBJECTIVE: The physical and chemical characteristics of the titanium implant surface have been shown to influence dental implant fixation. However, the underlying mechanism by which sandblasted, large-grit, acid-etched (SLA) treatment affects osseointegration remains elusive. METHODS: In the present study, the involved target genes and pathways for SLA treatment, which is an extensively used implant surface modification on improving osseointegration, were identified by in vitro microarray and bioinformatics analyses...
January 2016: Archives of Oral Biology
Andrew Kowalski, Julio Cabrera, Samih Nasr, Edgar Lerma
Amyloidosis results from the pathologic deposition of beta pleated sheet fibrils within various organs including the kidney. Most often, the deposition is composed of the well-known monoclonal immunoglobulin light chains (AL) or serum amyloid A protein (AA). Recently, a new type of amyloidogenic protein was discovered, leukocyte chemotactic factor 2 (LECT2). This type of amyloid tends to have an affinity to kidney and liver and is recognized as a distinct clinico-pathologic type of amyloidosis, presenting with varying degrees of impaired kidney function and proteinuria...
October 2015: Clinical Nephrology
Hwan-Jin Hwang, Tae Woo Jung, Baek-Hui Kim, Ho Cheol Hong, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Dong Seop Choi, Sei Hyun Baik, Hye Jin Yoo
Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently discovered hepatokine that mediates obesity-related metabolic disturbances. Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel therapeutic agents for inflammatory disorders including nonalcoholic fatty liver disease (NAFLD). However, no research has examined the connections or functions of LECT2 and the novel DPP-4 inhibitor, gemigliptin, in NAFLD pathogenesis. High-fat diet (HFD)-fed C57BL/6 mice were used to investigate the effect of gemigliptin on hepatic steatosis and LECT2 expression...
November 1, 2015: Biochemical Pharmacology
Sarah A Andres, Katie E Bickett, Mohammad A Alatoum, Theodore S Kalbfleisch, Guy N Brock, James L Wittliff
In contrast to studies focused on cigarette smoking and risk of breast cancer occurrence, this study explored the influence of smoking on breast cancer recurrence and progression. The goal was to evaluate the interaction between smoking history and gene expression levels on recurrence and overall survival of breast cancer patients. Multivariable Cox proportional hazards models were fitted for 48 cigarette smokers, 50 non-smokers, and the total population separately to determine which gene expressions and gene expression/cigarette usage interaction terms were significant in predicting overall and disease-free survival in breast cancer patients...
August 2015: Breast Cancer Research and Treatment
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