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Xiong-Jun Wang, Yunbo Qiao, Minzhe M Xiao, Lingbo Wang, Jun Chen, Wenjian Lv, Li Xu, Yan Li, Yumei Wang, Ming-Dian Tan, Chao Huang, Jinsong Li, Ting C Zhao, Zhaoyuan Hou, Naihe Jing, Y Eugene Chin
LIF promotes self-renewal of mouse embryonic stem cells (mESCs), and in its absence, the cells differentiate. LIF binds to the LIF receptor (LIFR) and activates the JAK-STAT3 pathway, but it remains unknown how the receptor complex triggers differentiation or self-renewal. Here, we report that the LIFR cytoplasmic domain contains a self-renewal domain within the juxtamembrane region and a differentiation domain within the C-terminal region. The differentiation domain contains four SPXX repeats that are phosphorylated by MAPK to restrict STAT3 activation; the self-renewal domain is characterized by a 3K motif that is acetylated by p300...
January 24, 2017: Cell Reports
Richard Leigh, Mahmoud M Mostafa, Elizabeth M King, Christopher F Rider, Suharsh Shah, Curtis Dumonceaux, Suzanne L Traves, Andrew McWhae, Tyler Kolisnik, Cora Kooi, Donna M Slater, Margaret M Kelly, Mark Bieda, Anna Miller-Larsson, Robert Newton
Although inhaled glucocorticoids, or corticosteroids (ICS), are generally effective in asthma, understanding their anti-inflammatory actions in vivo remains incomplete. To characterize glucocorticoid-induced modulation of gene expression in the human airways, we performed a randomized placebo-controlled crossover study in healthy male volunteers. Six hours after placebo or budesonide inhalation, whole blood, bronchial brushings, and endobronchial biopsies were collected. Microarray analysis of biopsy RNA, using stringent (≥2-fold, 5% false discovery rate) or less stringent (≥1...
August 2016: Pharmacology Research & Perspectives
Chih-Feng Yen, Shuen-Kuei Liao, S Joseph Huang, Selcuk Tabak, Felice Arcuri, Chyi-Long Lee, Aydin Arici, Felice Petraglia, Hsin-Shih Wang, Umit A Kayisli
BACKGROUND: Adenomyosis was found to have negative impacts on embryo implantation. Leukemia inhibitory factor (LIF), proposed to be a molecular marker for endometrial receptivity, works through the LIF receptor (LIFR) on both the embryo and the endometrium. We aimed to evaluate the endometrial expression of LIF and LIFR and its subsequent signaling in patients with adenomyosis during the window of implantation (WOI). METHODS: Endometrium was obtained during the WOI from patients with adenomyosis (age <45 years) who underwent hysterectomy and from age-matched controls who had no endometriosis or adenomyosis...
January 1, 2016: Reproductive Sciences
Hua-Jun Zhou, Xi Yang, Han-Jin Cui, Tao Tang, Jian-Hua Zhong, Jie-Kun Luo, A-Li Yang, Qi-Mei Zhang, Jing-Hua Zhou, Qiang Zhang
Reactive astrogliosis has occurred after intracerebral hemorrhage (ICH). Leukemia inhibitory factor (LIF) can act as a modulator for glial gene expression. Signal transducer and activator of transcription 3 (STAT3) is a critical regulator of reactive astrogliosis. The present study tested whether endogenous LIF acted on ICH-induced reactive astrogliosis via the STAT3 signaling pathway. Rats were divided into three experimental groups: 1) Rats received either an ICH or a needle insertion (sham), 2) Rats received 100 ng LIF or an equal volume of phosphate-buffered saline (PBS) by direct infusion into the lateral ventricle (LV) after ICH, and 3) AG490 (0...
December 20, 2016: Journal of Neurotrauma
Rachelle W Johnson, Elizabeth C Finger, Monica M Olcina, Marta Vilalta, Todd Aguilera, Yu Miao, Alyssa R Merkel, Joshua R Johnson, Julie A Sterling, Joy Y Wu, Amato J Giaccia
No abstract text is available yet for this article.
October 27, 2016: Nature Cell Biology
Rachelle W Johnson, Elizabeth C Finger, Monica M Olcina, Marta Vilalta, Todd Aguilera, Yu Miao, Alyssa R Merkel, Joshua R Johnson, Julie A Sterling, Joy Y Wu, Amato J Giaccia
Breast cancer cells frequently home to the bone marrow, where they may enter a dormant state before forming a bone metastasis. Several members of the interleukin-6 (IL-6) cytokine family are implicated in breast cancer bone colonization, but the role for the IL-6 cytokine leukaemia inhibitory factor (LIF) in this process is unknown. We tested the hypothesis that LIF provides a pro-dormancy signal to breast cancer cells in the bone. In breast cancer patients, LIF receptor (LIFR) levels are lower with bone metastases and are significantly and inversely correlated with patient outcome and hypoxia gene activity...
September 19, 2016: Nature Cell Biology
Hanlin Zeng, Jia Qu, Nan Jin, Jun Xu, Chenchu Lin, Yi Chen, Xinying Yang, Xiang He, Shuai Tang, Xiaojing Lan, Xiaotong Yang, Ziqi Chen, Min Huang, Jian Ding, Meiyu Geng
Histone deacetylase (HDAC) inhibitors have demonstrated clinical benefits in subtypes of hematological malignancies. However, the efficacy of HDAC inhibitors in solid tumors remains uncertain. This study takes breast cancer as a model to understand mechanisms accounting for limited response of HDAC inhibitors in solid tumors and to seek combination solutions. We discover that feedback activation of leukemia inhibitory factor receptor (LIFR) signaling in breast cancer limits the response to HDAC inhibition. Mechanistically, HDAC inhibition increases histone acetylation at the LIFR gene promoter, which recruits bromodomain protein BRD4, upregulates LIFR expression, and activates JAK1-STAT3 signaling...
September 12, 2016: Cancer Cell
Eun-Yeong Kim, Hee-Jung Choi, Tae-Wook Chung, Jun-Yong Choi, Hyung Sik Kim, Yeon-Seop Jung, Syng-Ook Lee, Ki-Tae Ha
The leaves and stems of Perilla frutescens var. acuta Kudo (PF) have been used to prevent threatened abortion in traditional medicine in the East Asian countries. Because reduced receptivity of endometrium is a cause of abortion, we analyzed the action of PF on the endometrial receptivity. PF increased the level of leukemia inhibitory factor (LIF), a major cytokine regulating endometrial receptivity, and LIF receptor in human endometrial Ishikawa cells. The PF-induced LIF expression was mediated by c-jun N-terminal kinase (JNK) and p38 pathways...
August 2016: Journal of Pharmacological Sciences
Emma C Walker, Rachelle W Johnson, Yifang Hu, Holly J Brennan, Ingrid J Poulton, Jian-Guo Zhang, Brendan J Jenkins, Gordon K Smyth, Nicos A Nicola, Natalie A Sims
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are IL-6 family members with a wide range of biological functions. Human OSM (hOSM) and murine LIF (mLIF) act in mouse cells via a LIF receptor (LIFR)-glycoprotein 130 (gp130) heterodimer. In contrast, murine OSM (mOSM) signals mainly via an OSM receptor (OSMR)-gp130 heterodimer and binds with only very low affinity to mLIFR. hOSM and mLIF stimulate bone remodeling by both reducing osteocytic sclerostin and up-regulating the pro-osteoclastic factor receptor activator of NF-κB ligand (RANKL) in osteoblasts...
October 7, 2016: Journal of Biological Chemistry
Ding Ma, Xiaoqian Jing, Baiyong Shen, Xinyu Liu, Xi Cheng, Bingrui Wang, Zhiping Fu, Chenghong Peng, Weihua Qiu
Pancreatic cancer (PC) is one of the leading causes of cancer-related deaths worldwide. Frequent metastasis and recurrence are the main reasons for the poor prognosis of PC patients. Thus, the discovery of new biomarkers and wider insights into the mechanisms involved in pancreatic tumorigenesis and metastasis is crucial. In the present study, we report that leukemia inhibitory factor receptor (LIFR) suppresses tumorigenesis and metastasis of PC cells both in vitro and in vivo. LIFR expression was significantly lower in PC tissues and was associated with local invasion (P=0...
August 2016: Oncology Reports
Débora Romeo Bertola, Rachel S Honjo, Wagner A R Baratela
Stüve-Wiedemann syndrome is a rare autosomal recessive disorder characterized by bowed long bones, joint restrictions, dysautonomia, and respiratory and feeding difficulties, leading to death in the neonatal period and infancy in several occasions. Since the first cases in 1971, much has been learned about this condition, including its molecular basis - mutations in the leukemia inhibitory factor receptor gene (LIFR) -, natural history and management possibilities. This review aims to highlight the clinical aspects, radiological features, molecular findings, and management strategies in Stüve-Wiedemann syndrome...
April 2016: Molecular Syndromology
Liam C Hunt, Jason White
Cytokines are an incredibly diverse group of secreted proteins with equally diverse functions. The actions of cytokines are mediated by the unique and sometimes overlapping receptors to which the soluble ligands bind. Classified within the interleukin-6 family of cytokines are leukemia inhibitory factor (LIF), oncostatin-M (OSM), cardiotrophin-1 (CT-1) and ciliary neurotrophic factor (CNTF). These cytokines all bind to the leukemia inhibitory factor receptor (LIFR) and gp130, and in some cases an additional receptor subunit, leading to activation of downstream kinases and transcriptional activators...
2016: Advances in Experimental Medicine and Biology
Anna Lange-Consiglio, Alessio Romaldini, Alessio Correani, Bruna Corradetti, Paola Esposti, Maria Francesca Cannatà, Claudia Perrini, Maria Giovanna Marini, Davide Bizzaro, Fausto Cremonesi
Recent studies have revealed the presence of a mesenchymal stem cell (MSC) population in human and in gilt granulosa cells (GCs), thus increasing the interest in identifying the same population in the bovine species. We first isolated GCs by scraping from bovine preovulatory follicles and then tested several different media to define the ideal conditions to select granulosa-derived stem cells. Although expressing MSC-associated markers, none of the media tested proven to be efficient in selecting MSC-like cells that were able to differentiate into mesodermic or ectodermic lineages...
April 2016: Cellular Reprogramming
Heather A Frey, Molly J Stout, Laurel N Pearson, Methodius G Tuuli, Alison G Cahill, Jerome F Strauss, Luis M Gomez, Samuel Parry, Jenifer E Allsworth, George A Macones
BACKGROUND: Preterm birth is considered a multifactorial condition; however, emerging evidence suggests that genetic variation among individuals may have an important role. Prior studies have suggested that single-nucleotide polymorphisms associated with genes related to the immune system, and particularly the maternal inflammatory response, may be associated with an increased risk of preterm delivery. OBJECTIVE: The objective of the study was to identify single-nucleotide polymorphisms associated with spontaneous preterm birth <37 weeks within a cohort of African-American women...
August 2016: American Journal of Obstetrics and Gynecology
Jie Yang, Shihui Qian, Xueting Cai, Wuguang Lu, Chunping Hu, Xiaoyan Sun, Yang Yang, Qiang Yu, S Paul Gao, Peng Cao
The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation...
June 2016: Molecular Cancer Therapeutics
Elavarasan Subramani, Ejimedo Madogwe, Chaitali Datta Ray, Subir Kumar Dutta, Baidyanath Chakravarty, Vilceu Bordignon, Raj Duggavathi, Koel Chaudhury
OBJECTIVE: To investigate the influence of dormant Mycobacterium tuberculosis on the expression of various endometrial receptivity markers and leukemia inhibitory factor (LIF)-signal transducers and activators of transcription 3 (STAT3) signaling pathway. Expression of endometrial receptivity markers and LIF-STAT3 signaling in in vitro decidualized human endometrial stromal cells (hESC) treated with 65 kDa mycobacterial heat shock protein (HSP65) is also explored. DESIGN: A prospective study...
April 2016: Fertility and Sterility
Amit Ghosh, Alip Ghosh, Somenath Datta, Debanjali Dasgupta, Soumyajit Das, Sukanta Ray, Subash Gupta, Simanti Datta, Abhijit Chowdhury, Raghunath Chatterjee, Saroj Kant Mohapatra, Soma Banerjee
Controversies about the origin of circulating miRNAs have encouraged us to identify organ specific circulating miRNAs as disease biomarkers. To identify liver-specific miRNAs for hepatocellular carcinoma (HCC), global expression profiling of miRNAs in liver tissue of HBV-HCC and HBV-control with no or mild fibrosis was evaluated. A total of 40 differentially expressed miRNAs were identified in HCC. Among ten highly altered miRNAs, six miRNAs were successfully validated in tissues, whereas only two miRNAs, miR-126 and miR-142-3p showed increased expression in plasma of HBV-HCC compared to HBV-non-HCC patients...
June 1, 2016: International Journal of Cancer. Journal International du Cancer
Li Wang, Jing Li, Hongying Zhao, Jing Hu, Yanyan Ping, Feng Li, Yujia Lan, Chaohan Xu, Yun Xiao, Xia Li
Crosstalk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. How long non-coding RNAs (lncRNAs) participate in the regulation of an abnormal pathway crosstalk in human cancer is largely unknown. Here, we proposed a strategy that integrates mRNA and lncRNA expression profiles for systematic identification of lncRNA-mediated crosstalk among risk pathways in different breast cancer subtypes. We identified 12 to 44 crosstalking pathway pairs mediated by 28 to 49 lncRNAs in four breast cancer subtypes...
March 2016: Molecular BioSystems
Kevin F Chau, Mark W Springel, Kevin G Broadbelt, Hye-Yeon Park, Salih Topal, Melody P Lun, Hillary Mullan, Thomas Maynard, Hanno Steen, Anthony S LaMantia, Maria K Lehtinen
After neural tube closure, amniotic fluid (AF) captured inside the neural tube forms the nascent cerebrospinal fluid (CSF). Neuroepithelial stem cells contact CSF-filled ventricles, proliferate, and differentiate to form the mammalian brain, while neurogenic placodes, which generate cranial sensory neurons, remain in contact with the AF. Using in vivo ultrasound imaging, we quantified the expansion of the embryonic ventricular-CSF space from its inception. We developed tools to obtain pure AF and nascent CSF, before and after neural tube closure, and to define how the AF and CSF proteomes diverge during mouse development...
December 21, 2015: Developmental Cell
Amélie Bourdiec, Syed-Furquan Ahmad, Asmaa Lachhab, Ali Akoum
The mechanisms involving the expression of interleukin (IL) 1 family members in the process of preparing the endometrium to receive an embryo remain unclear. In this study, decidualization differentially skewed the balance of IL1 family receptor expression in a pattern that increases endometrial stromal cell receptivity to IL1, IL18 and IL33. Additionally, endometrial cells showed increased expression of homeobox HOXA10 and HOXA11 and LIFR, which are known to be involved in endometrial embryo receptivity. Further analyses of decidual endometrial cells revealed a significant increase in the release of potent proinflammatory, remodelling and angiogenic factors implicated in the embryo invasion process, such as VEGF (P = 0...
January 2016: Reproductive Biomedicine Online
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