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Kynan T Lawlor, Luke Zappia, James Lefevre, Joo-Seop Park, Nicholas A Hamilton, Alicia Oshlack, Melissa H Little, Alexander Nicholas Combes
Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express Wnt4 , an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction...
January 24, 2019: ELife
Bing Mei, Ya Wang, Weiyuan Ye, Han Huang, Qian Zhou, Yuanyuan Chen, Yajing Niu, Manling Zhang, Qingyang Huang
Previous genome-wide linkage and association studies have identified an osteoporosis-associated locus at 1p36 that harbors SNPs rs34920465 and rs6426749. The 1p36 locus also comprises the WNT4 gene with known role in bone metabolism and functionally unknown ZBTB40/lncRNA ZBTB40-IT1 genes. How these might interact to contribute to osteoporosis susceptibility is not known. In this study, we show that lncRNA ZBTB40-IT1 is able to suppress osteogenesis and promote osteoclastogenesis by regulating the expression of WNT4, RUNX2, OSX, ALP, COL1A1, OPG and RANKL in U-2OS and hFOB1...
January 19, 2019: Human Genetics
M-L Lu, Y Zhang, J Li, Y Fu, W-H Li, G-F Zhao, X-H Li, L Wei, G-B Liu, H Huang
OBJECTIVE: Colorectal cancer (CRC) is the most common malignancy for cancer-associated death. This study aimed to investigate the effects of microRNA-124 (miR-124) on tumor proliferation of CRC in vivo and in vitro. MATERIALS AND METHODS: MiR-124 mimics were synthesized and transfected into SW620 cells, which were divided into SW620, microRNA-normal control (miR-NC) and miR-124 mimics group. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine miR-124, chemokine (C-C motif) ligand-20 (CCL20), tankyrase-2 (TNKS2), phospholipase Cbeta1 (PLCB1) and Wnt4...
January 2019: European Review for Medical and Pharmacological Sciences
Ping Zhou, Ying Li, Ruolin Di, Yi Yang, Songyan Meng, Fangfang Song, Lan Ma
OBJECTIVE: To investigate the mechanism of H19 on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: Ovariectomized (OVX) mouse model was established. RNA immunoprecipitation and RNA pull-down assays were performed to determine the correlation between H19 and forkhead box C2 (Foxc2). Chromatin immunoprecipitation assay was used to identify whether Foxc2 binds to the Wnt4 promoter region. Molecules expressions were measured by quantitative real-time polymerase chain reaction and western blot...
January 11, 2019: Journal of Cellular Physiology
Adam Chamberlin, Robert Huether, Aline Z Machado, Michael Groden, Hsiao-Mei Liu, Kinnari Upadhyay, Vivian O, Nathalia L Gomes, Antonio M Lerario, Mirian Y Nishi, Elaine M F Costa, Berenice Mendonca, Sorahia Domenice, Jacqueline Velasco, Johnny Loke, Harry Ostrer
Missense mutations in the gene, MAP3K1, are a common cause of 46,XY gonadal dysgenesis, accounting for 15-20% of cases (1). Functional studies demonstrated that all of these mutations cause a protein gain-of-function that alters co-factor binding and increases phosphorylation of the downstream MAP kinase pathway targets, MAPK11, MAP3K, and MAPK1. This dysregulation of the MAP kinase pathway results in increased CTNNB1, increased expression of WNT4 and FOXL2, and decreased expression of SRY and SOX9. Unique and recurrent pathogenic mutations cluster in three semi-contiguous domains outside the kinase region of the protein, a newly identified N-terminal domain that shares homology with Guanine Exchange Factor (GEF - residues Met164 to Glu231), a Plant HomeoDomain (PHD - residues Met442 to Trp495) and an ARMadillo repeat domain (ARM - residues Met566 to Glu862)...
January 4, 2019: Human Molecular Genetics
Zhe Huang, Mingli Yang, Yunze Li, Fan Yang, Yong Feng
Hypoxia is the most common characteristic of solid tumours driving cancer metastasis. Cancer cells release exosomes with various functions into the tumour microenvironment during cancer progression. However, the roles and associated mechanisms of hypoxic colorectal cancer (CRC) cell-derived exosomes remain poorly understood. Here, we found that exosomes secreted by hypoxic CRC cells promoted the migration and invasion abilities of normoxic CRC cells. Inhibition of exosome secretion by GW4869 reduced hypoxic exosome-mediated migration and invasion of normoxic CRC cells...
2018: International Journal of Biological Sciences
M R Nagaraja, Satya Prakash Gubbala, C R Wilma Delphine Silvia, Ramars Amanchy
We aimed to survey the monogenic causes of disorders of sex development (DSD) and thereby its prevalence in India. This study revealed mutations resulting in androgen insensitivity syndrome, 5α-reductase type 2 deficiency, and gonadal dysgenesis were commonly reported. Intriguingly, AR deficits were the most prevalent (32 mutations) and of 11/26 missense mutations were in exons 4-8 (encoding ligand binding domain). The unique features of SRD5A2 defects were p.R246Q (most prevalent) and p.G196S could be mutational hotspots, dual gene defects (p...
December 14, 2018: Systems Biology in Reproductive Medicine
Liying Fan, Yuan He, Jing Han, Puwei Ybuan, Xiong Guo, Weizhuo Wang
3'-Phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) has been shown to be important in the development of normal skeletal structure. The aim of the present study was to evaluate the role of PAPSS2 in the differentiation of chondrocytes as well as their mechanisms. Using RNA interference-mediated via a lentivirus and a retrovirus, PAPSS2 gene silence and overexpression in ATDC5 chondrogenic cells were performed. Chondrocyte differentiation and chondrogenic-related gene markers associated with extracellular matrix formation were noted...
December 2018: Experimental and Therapeutic Medicine
Wei Wu, Yanyin Han, Xiaoli Fan, Li Qinghu, Li Sun
The main pathological change of Parkinson's disease (PD) is progressive degeneration and necrosis of dopaminergic neurons in the midbrain, forming a Lewy body in many of the remaining neurons. Studies have found that in transgenic Drosophila, mutations in the PTEN-inducible kinase 1 (PINK1) gene may cause indirect flight muscle defects in Drosophila, and mitochondrial structural dysfunction as well. In this study, Wnt4 gene overexpression and knockdown were performed in PINK1 mutant PD transgenic Drosophila, and the protective effect of Wnt4 gene on PD transgenic Drosophila and its possible mechanism were explored...
December 11, 2018: International Journal of Neuroscience
Shengfang Qin, Xueyan Wang, Yunxing Li
OBJECTIVE: To explore the pathogenesis of a 46,XY female with sex reversal. METHODS: Peripheral blood lymphocytes of the patient were subjected to G-banding karyotype analysis. Sex chromosomes were analyzed with fluorescence in situ hybridization (FISH). SRY gene was analyzed by Sanger sequencing. The whole exome of the patient was subjected to next generation sequencing. Copy number variations (CNVs) of the NR0B1, SF1, SRY, SOX9 and WNT4 genes were validated by multiplex ligation-dependent probe amplification (MLPA)...
December 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Ashley Untereiner, Shaaban Abdo, Alpana Bhattacharjee, Himaben Gohil, Farzaneh Pourasgari, Neke Ibeh, Mi Lai, Battsetseg Batchuluun, Anthony Wong, Nicholas Khuu, Ying Liu, Dana Al Rijjal, Neil Winegarden, Carl Virtanen, Beverley A Orser, Over Cabrera, Gabor Varga, Jonathan Rocheleau, Feihan F Dai, Michael B Wheeler
γ-Aminobutyric acid (GABA) administration has been shown to increase β-cell mass, leading to a reversal of type 1 diabetes in mice. Whether GABA has any effect on β cells of healthy and prediabetic/glucose-intolerant obese mice remains unknown. In the present study, we show that oral GABA administration ( ad libitum) to mice indeed increased pancreatic β-cell mass, which led to a modest enhancement in insulin secretion and glucose tolerance. However, GABA treatment did not further increase insulin-positive islet area in high fat diet-fed mice and was unable to prevent or reverse glucose intolerance and insulin resistance...
December 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Daniel J Spade, Susan J Hall, Jeremy D Wortzel, Gerardo Reyes, Kim Boekelheide
Humans are universally exposed to low levels of phthalate esters (phthalates), which are used to plasticize polyvinyl chloride. Phthalates exert adverse effects on the development of seminiferous cords in the fetal testis through unknown toxicity pathways. To investigate the hypothesis that phthalates alter seminiferous cord development by disrupting retinoic acid signaling in the fetal testis, gestational day 15 fetal rat testes were exposed for 1-3 days to 10-6 M all-trans retinoic acid (ATRA) alone or in combination with 10-6 to 10-4 M mono-(2-ethylhexyl) phthalate (MEHP) in ex vivo culture...
November 26, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Junfeng Luo, Zhengda Lou, Junzheng Zheng
Bladder cancer is frequently occurred in urinary system and has complicated pathogenesis factors including both genetics and environmental factors that have not been fully illustrated. Hypoxia can further induce tumor progression. ROCK2 has abnormal expression in various tumors but its expression or functional role in bladder cancer have not been illustrated. In vitro cultured bladder cancer cell line T24 was randomly assigned into control group, hypoxia group (prepared under hypoxic culture), and ROCK2 siRNA group (transfected with ROCK2 siRNA after hypoxia treatment)...
November 11, 2018: Cancer Biomarkers: Section A of Disease Markers
Eda Becer, Duygu Yiğit Hanoğlu, Hilal Kabadayı, Azmi Hanoğlu, Seda Vatansever, Dudu Özkum Yavuz, Filiz Meriçli, Ali Hikmet Meriçli
OBJECTIVE: Colchicum pusillum belongs to the family Colchicaceae that particularly rich in tropolonic alkaloids. The aim of this study was to investigate the cytotoxicity and in vitro anticancer activity of Colchicum pusillum ethanolic extract on Colo-320 primer and Colo-741 metastatic colon adenocarcinoma cell lines. MATERIALS AND METHODS: Colchicum pusillum was collected and extracted with ethanol. Different concentrations of Colchicum pusillum extract were incubated for 24 h and 48 h with Colo-320 and Colo-741 cells...
November 17, 2018: Gene
Juanjuan Zhang, Penghua Zhang, Yunfeng Shen, Mei Yang, Hongxia Zou, Hongliang Liu
OBJECTIVE: In China, epithelial ovarian cancer (EOC) patients account for the majority of ovarian cancer patients. The pathogenesis of EOC, one of the most lethal gynecological malignancies, remains unclear. Recently, the role of WNT4 in gynecological disease and tumor development was reported, and a suspicious association of WNT4 with EOC was identified in Europeans. However, the contributions of the WNT4 gene to EOC and the underlying molecular mechanisms remains largely unknown. To determine whether the WNT4 gene is associated with EOC, this study investigated polymorphisms of the WNT4 gene in Han Chinese individuals...
November 17, 2018: Genetic Testing and Molecular Biomarkers
Michelle E Kossack, Samantha K High, Rachel E Hopton, Yi-Lin Yan, John H Postlethwait, Bruce W Draper
In laboratory strains of zebrafish, sex determination occurs in the absence of a typical sex chromosome and it is not known what regulates the proportion of animals that develop as males or females. Many sex determination and gonad differentiation genes that act downstream of a sex chromosome are well conserved among vertebrates, but studies that test their contribution to this process have mostly been limited to mammalian models. In mammals, WNT4 is a signaling ligand that is essential for ovary and Müllerian duct development, where it antagonizes the male-promoting FGF9 signal...
November 16, 2018: Genetics
Kai Zhang, Jin Xu, Zhiwei Zhang, Yu Huang, Zhiqiang Ruan, Shuyin Chen, Fei Zhu, Xinxin You, Chaofeng Jia, Qian Meng, Ruobo Gu, Xueqiang Lin, Junmin Xu, Pao Xu, Zhiyong Zhang, Qiong Shi
Protandrous black porgy (Acanthopagrus schlegelii) is a popular and valuable commercial marine fish in China and East Asian countries. Controlling and managing its breeding has been an imperative step towards obtaining a sustainable supply of this fish in aquaculture production systems. Therefore, study on the molecular mechanisms of sex change in black porgy has both scientific and commercial importance. Previously, we identified some candidate genes related to sex determination and differentiation from a high-quality genome assembly of the black porgy...
November 12, 2018: Genomics
Mikko Hallman, Antti Haapalainen, Johanna M Huusko, Minna K Karjalainen, Ge Zhang, Louis J Muglia, Mika Rämet
Spontaneous preterm birth is a serious and common pregnancy complication associated with hormonal dysregulation, infection, inflammation, immunity, rupture of fetal membranes, stress, bleeding, and uterine distention. Heredity is 25-40% and mostly involves the maternal genome, with contribution of the fetal genome. Significant discoveries of candidate genes by genome-wide studies and confirmation in independent replicate populations serve as signposts for further research. The main task is to define the candidate genes, their roles, localization, regulation, and the associated pathways that influence the onset of human labor...
September 18, 2018: Pediatric Research
Caroline Ripp, Julia Loth, Iveta Petrova, Karen Linnemannstöns, Monique Ulepic, Lee Fradkin, Jasprien Noordermeer, Andreas Wodarz
Wnt ligands are secreted glycoproteins that control many developmental processes and are crucial for homeostasis of numerous tissues in the adult organism. Signal transduction of Wnts involves the binding of Wnts to receptor complexes at the surface of target cells. These receptor complexes are commonly formed between a member of the Frizzled family of seven-pass transmembrane proteins and a co-receptor, which is usually a single-pass transmembrane protein. Among these co-receptors are several with structural homology to receptor tyrosine kinases, including Ror, PTK7, Ryk and MUSK...
November 2, 2018: Biology Open
Li-Yin Hung, Debasish Sen, Taylor K Oniskey, Jeremey Katzen, Noam A Cohen, Andrew E Vaughan, Wildaliz Nieves, Anatoly Urisman, Michael F Beers, Matthew F Krummel, De'Broski R Herbert
Coordinated efforts between macrophages and epithelia are considered essential for wound healing, but the macrophage-derived molecules responsible for repair are poorly defined. This work demonstrates that lung macrophages rely upon Trefoil factor 2 to promote epithelial proliferation following damage caused by sterile wounding, Nippostrongylus brasiliensis or Bleomycin sulfate. Unexpectedly, the presence of T, B, or ILC populations was not essential for macrophage-driven repair. Instead, conditional deletion of TFF2 in myeloid-restricted CD11cCre TFF2 flox mice exacerbated lung pathology and reduced the proliferative expansion of CD45- EpCAM+ pro-SPC+ alveolar type 2 cells...
January 2019: Mucosal Immunology
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