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Gustavo José Leirós, Julieta María Ceruti, María Lía Castellanos, Ana Gabriela Kusinsky, María Eugenia Balañá
In androgenetic alopecia, androgens impair dermal papilla-induced hair follicle stem cell (HFSC) differentiation inhibiting Wnt signaling. Wnt agonists/antagonists balance was analyzed after dihydrotestosterone (DHT) stimulation in androgen-sensitive dermal papilla cells (DPC) cultured as spheroids or monolayer. In both culture conditions, DHT stimulation downregulated Wnt5a and Wnt10b mRNA while the Wnt antagonist Dkk-1 was upregulated. Notably, tissue architecture of DPC-spheroids lowers Dkk-1 and enhances Wnt agonists' basal expression; probably contributing to DPC inductivity...
October 18, 2016: Molecular and Cellular Endocrinology
Takeshi Harada, Hideki Yamamoto, Shosei Kishida, Michiko Kishida, Chihiro Awada, Toshifumi Takao, Akira Kikuchi
Wnt5b, a member of the same family of proteins as Wnt5a of which overexpression is associated with cancer aggressiveness, is suggested to be involved in cancer progression, however details remain unclarified. We analyzed biochemical properties of purified Wnt5b and the mode of secretion of Wnt5b by cancer cells. Wnt5b was glycosylated at three asparagine residues and lipidated at one serine residue, and these post-translational modifications of Wnt5b are essential for secretion. Purified Wnt5b showed Dvl2 phosphorylation and Rac activation abilities to a similar extent as Wnt5a...
October 20, 2016: Cancer Science
Li Qin, Chan Liu, Ya-Guang Ni, Ya-Ning Shi, Bao-Xue Ao, Zheng Liu, Duan-Fang Liao
OBJECTIVE: Hypertension is closely associated with profound vascular remodeling, especially proliferation and hyperplasia of vascular smooth muscle cells (VSMCs). Aberrant Wnt5a signaling has been related to vascular diseases, but its role on the proliferation of VSMCs is unclear. The study evaluated the effect of Wnt5a on the proliferation of VSMCs and its possible mechanism. DESIGN AND METHOD: The capability of cell proliferation was detected by the assays of MTT, colony formation and EdU cell proliferation...
September 2016: Journal of Hypertension
Hidenori Nishihara, Naoki Kobayashi, Chiharu Kimura-Yoshida, Kuo Yan, Olga Bormuth, Qiong Ding, Akiko Nakanishi, Takeshi Sasaki, Mika Hirakawa, Kenta Sumiyama, Yasuhide Furuta, Victor Tarabykin, Isao Matsuo, Norihiro Okada
Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate...
October 2016: PLoS Genetics
Heather Marion Ames, Ming Yuan, Maria Adelita Vizcaíno, Wayne Yu, Fausto J Rodriguez
Low-grade (WHO I-II) gliomas and glioneuronal tumors represent the most frequent primary tumors of the central nervous system in children. They often have a good prognosis following total resection, however they can create many neurological complications due to mass effect, and may be difficult to resect depending on anatomic location. MicroRNAs have been identified as molecular regulators of protein expression/translation that can repress multiple mRNAs concurrently through base pairing, and have an important role in cancer, including brain tumors...
October 14, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Zhengxing Ge, Bo Li, Xun Zhou, Yi Yang, Jun Zhang
Chronic obstructive pulmonary disease (COPD) is featured by aberrant extracellular matrix (ECM) deposition. Trigger of the β-catenin/RhoA pathway has been involved in aberrant ECM deposition in several diseases. We investigated WNT signaling activation in primary pulmonary fibroblasts of rats with and without COPD and the function of WNT signaling in pulmonary fibroblast. We evaluated the expression of WNT signaling and the role of β-catenin, using MRC-5 fibroblasts and primary lung fibroblasts of rats with and without COPD...
October 13, 2016: Molecular and Cellular Biochemistry
M Phan, F Conte, K D Khandelwal, C W Ockeloen, T Bartzela, T Kleefstra, H van Bokhoven, M Rubini, H Zhou, C E L Carels
Tooth agenesis and orofacial clefts represent the most common developmental anomalies and their co-occurrence is often reported in patients as well in animal models. The aim of the present systematic review is to thoroughly investigate the current literature (PubMed, EMBASE) to identify the genes and genomic loci contributing to syndromic or non-syndromic co-occurrence of tooth agenesis and orofacial clefts, to gain insight into the molecular mechanisms underlying their dual involvement in the development of teeth and facial primordia...
December 2016: Human Genetics
Yiming Zhang, Zhao Liu, Min Zhou, Changjian Liu
Aberrant smooth muscle cells (SMCs) play important roles in the formation of abdominal aortic aneurysm (AAA). Although the molecular mechanism of AAA formation has been investigated, there is a lack of understanding concerning the role of microRNAs (miRNAs) in AAA, which the current study aimed to address. Firstly, miRNA array analysis was performed in order to compare the miRNA profiles in a mouse model of AAA with those in normal control mice, and differentially expressed miRNAs were identified. miR-129-5p was selected for further analysis, and was used to transfect human SMCs...
October 2016: Experimental and Therapeutic Medicine
Pedro Cisternas, Paulina Salazar, Carmen Silva-Álvarez, L Felipe Barros, Nibaldo C Inestrosa
In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters...
2016: Neural Plasticity
Melissa G Farb, Shakun Karki, Song-Young Park, Samantha M Saggese, Brian Carmine, Donald T Hess, Caroline Apovian, Jessica L Fetterman, Rosa Bretón-Romero, Naomi M Hamburg, José J Fuster, María A Zuriaga, Kenneth Walsh, Noyan Gokce
Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m(2)) and five metabolically normal non-obese (BMI 26±2 kg/m(2)) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses...
September 28, 2016: Vascular Medicine
Fumio Goto, Sei Kakinuma, Masato Miyoshi, Tomoyuki Tsunoda, Shun Kaneko, Ayako Sato, Yu Asano, Satoshi Otani, Seishin Azuma, Hiroko Nagata, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Mina Nakagawa, Yasuhiro Asahina, Mamoru Watanabe
AIM: Fetal hepatic stem/progenitor cells, called hepatoblasts, play central roles in liver organogenesis; however, molecular mechanisms regulating proliferation and terminal differentiation of such cells have not been completely elucidated. Bone morphogenetic protein-4 (BMP-4) is essential for the development of stem cells in various tissues, but its function in regulating the phenotype of hepatoblasts after mid-gestational fetal stage remains unclear. The aim of this study is to clarify a functional role for BMP-4 in proliferation and terminal differentiation of murine hepatoblasts in mid-gestational fetal livers...
September 27, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Chih-Wen Chu, Sergei Y Sokol
The coordinated orientation of cells across the tissue plane, known as planar cell polarity (PCP), is manifested by the segregation of core PCP proteins to different sides of the cell. Secreted Wnt ligands are involved in many PCP-dependent processes, yet whether they act as polarity cues has been controversial. We show that in Xenopus early ectoderm, the Prickle3/Vangl2 complex was polarized to anterior cell edges and this polarity was disrupted by several Wnt antagonists. In midgastrula embryos, Wnt5a, Wnt11, and Wnt11b, but not Wnt3a, acted across many cell diameters to orient Prickle3/Vangl2 complexes away from their sources regardless of their positions relative to the body axis...
September 23, 2016: ELife
Jiajia Jin, Ping Zhan, Hong Qian, Xiaoxia Wang, Masaru Katoh, Kevin Phan, Jin-Haeng Chung, Tangfeng Lv, Yong Song
BACKGROUND: Wingless-type protein (Wnt) signaling pathway plays a crucial role in the development of human malignancies, such as epithelial-to-mesenchymal transition (EMT) and the maintenance of cancer stem cells (CSCs). Several studies have shown that the expression levels of Wnt proteins, ligands of Wnt signaling pathway, are related to clinical outcomes of non-small cell lung cancer (NSCLC) patients. This meta-analysis aimed to assess the prognostic value of Wnts proteins in patients with NSCLC...
August 2016: Translational Lung Cancer Research
Jing Zhang, Yiru Shao, Daikun He, Lin Zhang, Guoxiong Xu, Jie Shen
: An increase in epithelial cell permeability has been proposed to contribute to phosgene-induced acute lung injury (ALI). However, no specific and effective means for blocking increases in permeability are currently available. Cell-based therapy using bone marrow-derived mesenchymal stem cells (MSCs) is an attractive new approach. Canonical wnt/β-catenin signaling has been demonstrated to contribute to both epithelial cell injury and repair mechanisms in ALI. The goal of our study was to determine the effects of MSCs on epithelial permeability in phosgene-induced ALI in Sprague-Dawley (SD) rats and identify changes in major components of the wnt3a/β-catenin signaling pathway during this process...
October 2016: Inhalation Toxicology
Li Qin, Chan Liu, Ya-Guang Ni, Ya-Ning Shi, Bao-Xue Ao, Zheng Liu, Duan-Fang Liao
OBJECTIVE: Hypertension is closely associated with profound vascular remodeling, especially proliferation and hyperplasia of vascular smooth muscle cells (VSMCs). Aberrant Wnt5a signaling has been related to vascular diseases, but its role on the proliferation of VSMCs is unclear. The study evaluated the effect of Wnt5a on the proliferation of VSMCs and its possible mechanism. DESIGN AND METHOD: The capability of cell proliferation was detected by the assays of MTT, colony formation and EdU cell proliferation...
September 2016: Journal of Hypertension
Silvia Mazzotta, Carlos Neves, Rory J Bonner, Andreia S Bernardo, Kevin Docherty, Stefan Hoppler
Wnt signaling is a key regulator of vertebrate heart development; however, specific roles for human cardiomyocyte development remain uncertain. Here we use human embryonic stem cells (hESCs) to analyze systematically in human cardiomyocyte development the expression of endogenous Wnt signaling components, monitor pathway activity, and dissect stage-specific requirements for canonical and noncanonical Wnt signaling mechanisms using small-molecule inhibitors. Our analysis suggests that WNT3 and WNT8A, via FZD7 and canonical signaling, regulate BRACHYURY expression and mesoderm induction; that WNT5A/5B, via ROR2 and noncanonical signaling, regulate MESP1 expression and cardiovascular development; and that later in development WNT2, WNT5A/5B, and WNT11, via FZD4 and FZD6, regulate functional cardiomyocyte differentiation via noncanonical Wnt signaling...
October 11, 2016: Stem Cell Reports
Wang-Dong Xu, Jia Wang, Tong-Ling Yuan, Yan-Hong Li, Hang Yang, Yi Liu, Yi Zhao, Martin Herrmann
Antigen-presenting dendritic cells interpret environmental signals to orchestrate local and systemic immune responses. In this study, the roles of Wnt proteins and their signaling pathway members in the maturation and function of monocyte-derived DCs were investigated. The present study showed higher expression of β-catenin, as well as pGSK-3β in DCs than those in monocytes. Wnt3a, Wnt5a and inhibition of GSK-3β promoted differentiation of DCs, but inhibited maturation of DCs. GSK-3β induced DCs maturation with unconventional phenotypes...
September 8, 2016: Cellular Immunology
Nobuaki Ozeki, Naoko Hase, Naoya Higuchi, Taiki Hiyama, Hideyuki Yamaguchi, Rie Kawai, Toru Matsumoto, Kazuhiko Nakata, Makio Mogi
While human induced pluripotent stem (hiPS) cells have potential use in regenerative medicine, there are no reports on odontoblastic differentiation of hiPS cells. In the current study, to examine integrin profiles and explore the early signaling cascade of odontoblastic differentiation in hiPS cells, we investigated the regulation of autophagy-related gene (Atg) and wingless/int1 (Wnt) signaling in gelatin scaffold (GS) combined with bone morphogenetic protein (BMP)-4 (GS/BMP-4)-mediated odontoblastic differentiation...
September 15, 2016: Differentiation; Research in Biological Diversity
Smitha Bhat, Sandeep Mallya, Vinay Koshy Varghese, Pradyumna Jayaram, Sanjiban Chakrabarty, Kalpana S Joshi, Tanuja M Nesari, Kapaettu Satyamoorthy
With a purpose of accurate and simultaneous determination of DNA methylation from multiple loci in multiple samples, here, we are demonstrating a method to aid rapid DNA methylation detection of genomic sequences. Using genomic DNA of peripheral blood from 14 healthy individuals, DNA methylation in 465 CpG sites from 12 loci of genes (ADAM22, ATF2, BCR, CD83, CREBBP, IL12B, IL17RA, MAP2K2, RBM38, TGFBR2, TGFBR3, and WNT5A) was analysed by targeted next generation bisulfite sequencing. Analysed region for three genes, BCR, IL17RA and RBM38 showed an absolute mean DNA methylation of 25...
December 15, 2016: Gene
Chandra Prakash Prasad, Shivendra Kumar Chaurasiya, William Guilmain, Tommy Andersson
BACKGROUND: WNT5A (-/-) mammary tissue has been shown to exhibit increased ductal elongation, suggesting elevated mammary cell migration. Increased epithelial cell migration/invasion has often but not always been linked to the epithelial-mesenchymal transition (EMT). In the current study, we investigated the loss of WNT5A in HB2 human mammary epithelial cells and hypothesized that this loss increased their invasion via the EMT. Based on these results, we postulated that suppression of breast cancer cell migration and invasion by WNT5A is due to EMT reversal...
2016: Journal of Experimental & Clinical Cancer Research: CR
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