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Wang Song, Liu Qian, Guo Jing, Feng Jie, Shan Xiaosong, Liu Chunhui, Li Yangfang, Li Guilin, Hua Gao, Zhang Yazhuo
Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (p = 0...
March 16, 2018: Molecular and Cellular Endocrinology
Toshiaki Teratani, Kengo Tomita, Takahiro Suzuki, Hirotaka Furuhashi, Rie Irie, Makoto Nishikawa, Junji Yamamoto, Toshifumi Hibi, Soichiro Miura, Tohru Minamino, Yuichi Oike, Ryota Hokari, Takanori Kanai
Incidence of nonalcoholic steatohepatitis (NASH), which is considered a hepatic manifestation of metabolic syndrome, has been increasing worldwide with the rise in obesity; however, its pathological mechanism is poorly understood. Here, we demonstrate that the hepatic expression of aortic carboxypeptidase-like protein (ACLP), a glycosylated, secreted protein, increases in NASH in humans and mice. Furthermore, we elucidate that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology...
March 19, 2018: Journal of Clinical Investigation
Jiadela Teliewubai, Bin Bai, Yiwu Zhou, Yuyan Lu, Shikai Yu, Chen Chi, Jue Li, Jacques Blacher, Yawei Xu, Yi Zhang
Objective: Secreted frizzled related protein 5 (SFRP5) is a novel anti-inflammatory adipokine that is implicated in metabolic and cardiovascular disease (CVD). However, little is known about the relevance of SFRP5 with asymptomatic hypertensive target organ damages (TODs). We aimed to investigate the association between SFRP5 and TOD in a large population. Clinical trial registration: NCT02368938. Methods: A total of 1,745 community-dwelling elderly subjects aged over 65 years from northern Shanghai were recruited in the study...
2018: Clinical Interventions in Aging
Harriet C Fitzgerald, Jemma Evans, Nicholas Johnson, Giuseppe Infusini, Andrew Webb, Luk J R Rombauts, Beverley J Vollenhoven, Lois A Salamonsen, Tracey A Edgell
The regenerative, proliferative phase of a woman's menstrual cycle is a critical period which lays the foundation for the subsequent, receptive secretory phase. Although endometrial glands and their secretions are essential for embryo implantation and survival, the proliferative phase, when these glands form, has been rarely examined. We hypothesized that alterations in the secreted proteome of the endometrium of idiopathic infertile women would reflect a disturbance in proliferative phase endometrial regeneration...
March 13, 2018: Biology of Reproduction
Kingsley K Duah, Edward K Essuman, Osca S Olympio, Worlah Akwetey, Vida Gyimah, Jeremiah O Yeboah
Commercial poultry production, although fairly well developed, continues to develop rapidly in Africa and other areas of the world. The local chickens, which may perhaps be harnessed and exploited for poverty alleviation, form part of the many local assets of underprivileged people living in the rural areas. In view of this, the study aims to investigate consumer acceptability of indigenous chicken meats using survey and sensory evaluation. The survey is comprised mainly of interviewing market women and supplying birds to them for sale in order to find answers to questions related to marketability or otherwise of the naked-neck, frizzled naked-neck, and normal-feathered cockerels...
March 8, 2018: Poultry Science
Xiaobin Huang, Janine N Post, Leilei Zhong, Jeroen Leijten, Staffan Larsson, Marcel Karperien, André Struglics
OBJECTIVE: To explore the involvement of the WNT and BMP antagonists Dickkopf-related protein 1 (DKK1), Frizzled-related protein (FRZB) and Gremlin 1 (GREM1) in knee injury and osteoarthritis (OA). DESIGN: The antagonists were immunoassayed in synovial fluid from a cross-sectional cohort of 9 knee healthy reference subjects, patients with recent (0-77 days, n=158) or old (1-37 years, n=50) knee injuries, and OA (n=22). Cartilage (ARGS-aggrecan, cartilage oligomeric matrix protein and C2C type II collagen) and other biomarkers were assessed in synovial fluid in a subset of samples...
March 8, 2018: Osteoarthritis and Cartilage
Salvatore Condello, Livia Elena Sima, Cristina Ivan, Horacio Cardenas, Gary E Schiltz, Rama K Mishra, Daniela Matei
Cancer progression and recurrence are linked to a rare population of cancer stem cells (CSC). Here we hypothesized that interactions with the extracellular matrix drive CSC proliferation and tumor-initiating capacity and investigated the functions of scaffold protein tissue transglutaminase (TG2) in ovarian CSC. Complexes formed by TG2, fibronectin (FN), and integrin β1 were enriched in ovarian CSC and detectable in tumors. A function-inhibiting antibody against the TG2 FN-binding domain suppressed complex formation, CSC proliferation as spheroids, tumor-initiating capacity, and stemness-associated Wnt/β-catenin signaling...
March 6, 2018: Cancer Research
Hsiu-Kuan Lin, Hsi-Hui Lin, Yu-Wei Chiou, Ching-Lung Wu, Wen-Tai Chiu, Ming-Jer Tang
Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-RasV12 gene) transformation by Ha-RasV12 . Cav1 overexpression abrogates the Ha-RasV12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells...
March 4, 2018: Journal of Cellular and Molecular Medicine
Yanpeng Ci, Xiaoning Li, Maorong Chen, Jiateng Zhong, Brian J North, Hiroyuki Inuzuka, Xi He, Yu Li, Jianping Guo, Xiangpeng Dai
Wnt signaling has emerged as a major regulator of tissue development by governing the self-renewal and maintenance of stem cells in most tissue types. As a key upstream regulator of the Wnt pathway, the transmembrane E3 ligase ZNRF3 has recently been established to play a role in negative regulation of Wnt signaling by targeting Frizzled (FZD) receptor for ubiquitination and degradation. However, the upstream regulation of ZNRF3, in particular the turnover of ZNRF3, is still unclear. Here we report that ZNRF3 is accumulated in the presence of proteasome inhibitor treatment independent of its E3-ubiquitin ligase activity...
March 1, 2018: Protein & Cell
Xiao-Song Yuan, Ming Zhang, Hui-Yan Wang, Jian Jiang, Bin Yu
By biochemical and epidemiological similarity with type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) has some overlap between prediction markers and risk factors of T2DM. The present study aimed to establish that secreted frizzled-related protein 4 (SFRP4) and ficolin-3 levels, which have been linked to insulin resistance and the development of T2DM, are elevated in GDM women. A longitudinal prospective cohort study of 86 GDM and 273 normal glucose tolerant (NGT) pregnant women was performed...
February 27, 2018: Endocrine Journal
Nicolas Aznar, Jason Ear, Ying Dunkel, Nina Sun, Kendall Satterfield, Fang He, Nicholas A Kalogriopoulos, Inmaculada Lopez-Sanchez, Majid Ghassemian, Debashis Sahoo, Irina Kufareva, Pradipta Ghosh
Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and heterotrimeric G proteins and associated GPCRs. Daple is a guanine nucleotide exchange factor (GEF) for the G protein Gαi Daple also binds to FZD and the Wnt/FZD mediator Dishevelled (Dvl), and it enhances β-catenin-independent Wnt signaling in response to Wnt5a-FZD7 signaling...
February 27, 2018: Science Signaling
Yan-Hua Wang, Yoichi Imai, Masayuki Shiseki, Junji Tanaka, Toshiko Motoji
Multidrug resistance (MDR) is a major obstacle to leukemia treatment. The Frizzled-1 (FZD1) Wnt receptor is involved in MDR in some solid cancers, but has rarely been reported to act in acute myeloid leukemia (AML). We investigated whether the knockdown of FZD1 affects MDR1 expression and P-glycoprotein (P-gp) function in multidrug resistant leukemic cell lines, as well as FZD1 and MDR1/P-gp expression in leukemic cells taken from patients with AML (n = 112). FZD1 knockdown significantly reduced MDR1 expression through the Wnt/β-catenin pathway, disrupted the P-gp efflux function, induced the recovery of sensitivity to chemotherapeutic agents, and hindered cell proliferation in cell lines...
January 31, 2018: Leukemia Research
Yuxiang Dai, Hao Lu, Shen Wang, Shufu Chang, Chenguang Li, Zheyong Huang, Feng Zhang, Hongbo Yang, Yi Shen, Zhangwei Chen, Juying Qian, Ge Junbo
BACKGROUND: In this work, we examined the angiogenic function of microRNA-216b in an in vitro rat diabetic model of myocardial microvascular endothelial cells (MMECs). METHODS: MMECs were extracted from Wistar rats (MMEC(WI)) or diabetic Goto-Kakizaki (GK) rats (MMEC(GK)) and cultured in vitro. QRT-PCR was applied to compare miR-216b between MMEC(WI) and MMEC(GK). MiR-216b was downregulated in MMEC(GK). Its effects on angiogenic development, including invasion and proliferation, were evaluated...
February 22, 2018: Gene
Timothy Mitchell, James W MacDonald, Sengkeo Srinouanpranchanh, Theodor K Bammler, Sean Merillat, Erica Boldenow, Michelle Coleman, Kathy Agnew, Audrey Baldessari, Jennifer E Stencel-Baerenwald, Jennifer Tisoncik-Go, Richard R Green, Michael J Gale, Lakshmi Rajagopal, Kristina M Adams Waldorf
BACKGROUND: Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. OBJECTIVE: The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development...
February 21, 2018: American Journal of Obstetrics and Gynecology
Ian Ackers, Candice Szymanski, K Jordan Duckett, Leslie A Consitt, Mitchell J Silver, Ramiro Malgor
BACKGROUND AND AIMS: Wnt5a is a highly studied member of the Wnt family and recently has been implicated in the pathogenesis of atherosclerosis, but its precise role is unknown. Foam cell development is a critical process to atherosclerotic plaque formation. In the present study, we investigated the role of noncanonical Wnt5a signaling in the development of foam cells. METHODS: Human carotid atherosclerotic tissue and THP-1-derived macrophages were used to investigate the contribution of Wnt5a signaling in the formation of foam cells...
February 20, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Paul McVeigh, Erin McCammick, Paul McCusker, Duncan Wells, Jane Hodgkinson, Steve Paterson, Angela Mousley, Nikki J Marks, Aaron G Maule
G protein-coupled receptors (GPCRs) are established drug targets. Despite their considerable appeal as targets for next-generation anthelmintics, poor understanding of their diversity and function in parasitic helminths has thwarted progress towards GPCR-targeted anti-parasite drugs. This study facilitates GPCR research in the liver fluke, Fasciola hepatica, by generating the first profile of GPCRs from the F. hepatica genome. Our dataset describes 147 high confidence GPCRs, representing the largest cohort of GPCRs, and the largest set of in silico ligand-receptor predictions, yet reported in any parasitic helminth...
February 5, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Guillaume Courbon, Raphaëlle Lamarque, Maude Gerbaix, Robin Caire, Marie-Thérèse Linossier, Norbert Laroche, Mireille Thomas, Thierry Thomas, Laurence Vico, Hubert Marotte
Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss...
February 22, 2018: Scientific Reports
Josué Curto, Beatriz Del Valle-Pérez, Aida Villarroel, Guillem Fuertes, Meritxell Vinyoles, Raúl Peña, Antonio García de Herreros, Mireia Duñach
Canonical and non-canonical Wnt pathways share some common elements but differ in the responses they evoke. Similar to Wnt ligands acting through the canonical pathway, Wnts that activate the non-canonical signaling, such as Wnt5a, promote Disheveled (Dvl) phosphorylation and its binding to the Frizzled (Fz) Wnt receptor complex. The protein kinase CK1ε is required for Dvl/Fz association in both canonical and non-canonical signaling. Here we show that differently to its binding to canonical Wnt receptor complex, CK1ε does not require p120-catenin for the association with the Wnt5a co-receptor Ror2...
February 21, 2018: Molecular Oncology
Zora Lasabova, Andrea Stanclova, Marian Grendar, Silvia Mikolajcikova, Andrea Calkovska, Nina Lenhartova, Peter Ziak, Katarina Matasova, Martin Caprnda, Peter Kruzliak, Mirko Zibolen
BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease occurring in preterm neonates, caused by incorrect development of retinal blood vessels. It has been suggested that, in addition to gestational age, weight, and oxygen supplementation, genetic factors can play a role in the pathogenesis of ROP. METHODS: In the present prospective study, 97 neonates were enrolled based on the gestational age and weight, and genomic DNA from patients diagnosed with ROP and premature newborns without ROP was collected...
February 21, 2018: Ophthalmic Genetics
T Heinosalo, M Gabriel, L Kallio, P Adhikari, K Huhtinen, T D Laajala, E Kaikkonen, A Mehmood, P Suvitie, H Kujari, T Aittokallio, A Perheentupa, M Poutanen
STUDY QUESTION: What is the role of SFRP2 in endometriosis? SUMMARY ANSWER: SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis, regulating endometriosis lesion growth and indicating endometriosis lesion borders together with CTNNB1 (also known as beta catenin). WHAT IS KNOWN ALREADY: Endometriosis is a common, chronic disease that affects women of reproductive age, causing pain and infertility, and has significant economic impact on national health systems...
February 15, 2018: Human Reproduction
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