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Clemens L Bockmeyer, Juliane Wittig, Karen Säuberlich, Philipp Selhausen, Marc Eßer, Philip Zeuschner, Friedrich Modde, Kerstin Amann, Christoph Daniel
BACKGROUND: Glomeruli are excellent pre-determined natural structures for laser micro-dissection. Compartment-specific glomerular gene expression analysis of formalin-fixed paraffin-embedded renal biopsies could improve research applications. The major challenge for such studies is to obtain good-quality RNA from small amounts of starting material, as applicable for the analysis of glomerular compartments. In this work, we provide data and recommendations for an optimized workflow of glomerular mRNA analysis...
March 13, 2018: BMC Molecular Biology
Herui Wang, Chi Zhang, Xiaowen Wang, Yaru Lian, Bin Guo, Miao Han, Xiaoe Zhang, Xiaoting Zhu, Sixian Xu, Zengli Guo, Yunli Bi, Qian Shen, Xiang Wang, Jiaojiao Liu, Yuan Zhuang, Ting Ni, Hong Xu, Xiaohui Wu
Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common developmental defects in humans. Despite of several known CAKUT-related loci ( HNF1B , PAX2 , EYA1 , etc.), the genetic etiology of CAKUT remains to be elucidated for most patients. In this study, we report that disruption of the Holliday Junction resolvase gene Gen1 leads to renal agenesis, duplex kidney, hydronephrosis, and vesicoureteral reflux (VUR) in mice. GEN1 interacts with SIX1 and enhances the transcriptional activity of SIX1/EYA1, a key regulatory complex of the GDNF morphogen...
2018: International Journal of Biological Sciences
Diana A van der Plaat, Kim de Jong, Maaike de Vries, Cleo C van Diemen, Ivana Nedeljković, Najaf Amin, Hans Kromhout, Roel Vermeulen, Dirkje S Postma, Cornelia M van Duijn, H Marike Boezen, Judith M Vonk
OBJECTIVES: Occupational pesticide exposure is associated with a wide range of diseases, including lung diseases, but it is largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational exposure to pesticides and genome-wide DNA methylation sites. METHODS: 1561 subjects of LifeLines were included with either no (n=1392), low (n=108) or high (n=61) exposure to any type of pesticides (estimated based on current or last held job)...
February 19, 2018: Occupational and Environmental Medicine
Colin J R Stewart, Susan Bigby, Tino Giardina, Fabienne Grieu-Iacopetta, Benhur Amanuel
Papillary proliferations of the endometrium (PPEs) are uncommon lesions that are often associated with endometrial polyps. PPEs occasionally precede or co-exist with atypical endometrial hyperplasia or adenocarcinoma, but their pathogenesis and relationship to endometrial neoplasia is uncertain. In the present study 11 PPEs, including eight benign papillary proliferations (BPPs) and three complex papillary hyperplasias (CPHs) were examined immunohistochemically for expression of PAX2, BAF250a, p16, β-catenin and DNA mismatch repair (MMR) proteins...
February 12, 2018: Pathology
Yaqing Wang, Li Wang, Yujuan Zhu, Jianhua Qin
Nicotine has been recognized to trigger various neuronal disabilities in the fetal brain and long-lasting behavioral deficits in offspring. However, further understanding of fetal brain development under nicotine exposure is challenging due to the limitations of existing animal models. Here, we create a new brain organoid-on-a-chip system derived from human induced pluripotent stem cells (hiPSCs) that allows us to model neurodevelopmental disorders under prenatal nicotine exposure (PNE) at early stages. The brain organoid-on-a-chip system facilitates 3D culture, in situ neural differentiation, and self-organization of brain organoids under continuous perfused cultures in a controlled manner...
February 13, 2018: Lab on a Chip
Lori L O'Brien, Qiuyu Guo, Emad Bahrami-Samani, Joo-Seop Park, Sean M Hasso, Young-Jin Lee, Alan Fang, Albert D Kim, Jinjin Guo, Trudy M Hong, Kevin A Peterson, Scott Lozanoff, Ramya Raviram, Bing Ren, Ben Fogelgren, Andrew D Smith, Anton Valouev, Andrew P McMahon
Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs...
January 29, 2018: PLoS Genetics
China Nagano, Kandai Nozu, Naoya Morisada, Masahiko Yazawa, Daisuke Ichikawa, Keita Numasawa, Hiroyo Kourakata, Chieko Matsumura, Satoshi Tazoe, Ryojiro Tanaka, Tomohiko Yamamura, Shogo Minamikawa, Tomoko Horinouchi, Keita Nakanishi, Junya Fujimura, Nana Sakakibara, Yoshimi Nozu, Ming Juan Ye, Hiroshi Kaito, Kazumoto Iijima
BACKGROUND: Comprehensive genetic approaches for diagnosing inherited kidney diseases using next-generation sequencing (NGS) have recently been established. However, even with these approaches, we are still failing to detect gene defects in some patients who appear to suffer from genetic diseases. One of the reasons for this is the difficulty of detecting copy number variations (CNVs) using our current approaches. For such cases, we can apply methods of array-based comparative genomic hybridization (aCGH) or multiplex ligation and probe amplification (MLPA); however, these are expensive and laborious and also often fail to identify CNVs...
January 25, 2018: Clinical and Experimental Nephrology
Dharmeshkumar Patel, Atsushi Shimomura, Sreeparna Majumdar, Matthew C Holley, Eri Hashino
The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor...
2018: PloS One
Abheepsa Mishra, Kamesh Ayasolla, Vinod Kumar, Xiqian Lan, Himanshu Vashistha, Rukhsana Aslam, Ali Hussain, Sheetal Chowdhary, Shadafarin Marashi Shoshtari, Nitpriya Paliwal, Waldemar Popik, Moin A Saleem, Ashwani Malhotra, Leonard G Meggs, Karl Skorecki, Pravin C Singhal
The loss of podocyte (PD) molecular phenotype is an important feature of diabetic podocytopathy. We hypothesized that high glucose (HG) induces dedifferentiation in differentiated podocytes (DPD) through alterations in APOL1-microRNA (miR) 193a axis. HG-induced DPDs dedifferentiation manifested in the form of down regulation of WT1 and upregulation of PAX2 expression. WT1- silenced DPDs displayed enhanced expression of PAX2. Immunoprecipitation (IP) of DPD cellular lysates with anti-WT1 antibody revealed formation of WT1 repressor complexes containing Polycomb group proteins (PcG), EZH2, Menin, and DNA methyl transferase (DNMT1), whereas, silencing of either WT1 or DNMT1 disrupted this complex with enhanced expression of PAX2...
January 10, 2018: American Journal of Physiology. Renal Physiology
Zahida Yesmin Roly, Brendan Backhouse, Andrew Cutting, Tiong Yang Tan, Andrew H Sinclair, Katie L Ayers, Andrew T Major, Craig A Smith
The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
Alberto Galvez-Ruiz, Anthony J Lehner, Alicia Galindo-Ferreiro, Patrik Schatz
Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an autosomal dominant disease characterised by the presence of congenital renal and optic nerve abnormalities associated with mutations of the PAX2 gene. In this article, the authors present four patients with PAPRS who are carriers of three new PAX2 mutations, as well as another patient with a possible non-pathogenic variant of the PAX2 gene. All patients were given a full neurophthalmological examination, and all patients underwent a genetic test for PAX2...
October 2017: Neuro-ophthalmology
James A Browne, Shih Hsing Leir, Scott Eggener, Ann Harris
Viral infections of the epididymis are associated with epididymitis, which damages the epithelium and impairs fertility. We showed previously that innate immune response genes were differentially expressed in the corpus and cauda region of the human epididymis in comparison to the caput. Here we investigate the antiviral defense response mechanisms of human epididymis epithelial (HEE) cells. Toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are enriched in HEE cells from the corpus and cauda region...
January 12, 2018: Molecular and Cellular Endocrinology
Carolyn A Morrison, Hao Chen, Tiffany Cook, Stuart Brown, Jessica E Treisman
Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs. The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye, and is maintained in both neuronal and non-neuronal cell types. Glass is required for neuronal progenitors to differentiate as photoreceptors, but its role in non-neuronal cone and pigment cells is unknown. To determine whether Glass activity is limited to neuronal lineages, we compared the effects of misexpressing it in neuroblasts of the larval brain and in epithelial cells of the wing disc...
January 11, 2018: PLoS Genetics
Xiu-Li Wang, Ling Hou, Cheng-Guang Zhao, Ying Tang, Bo Zhang, Jing-Ying Zhao, Yu-Bin Wu
AIM: To screen and verify downstream genes involved in the epithelial mesenchymal transition (EMT) induced by paired box 2 (PAX2) in NRK-52E cells. METHODS: NRK-52E cells were transfected with lentivirus carrying PAX2 gene or no-load virus respectively. Total RNA was isolated 72 hr after transfection from PAX2-overexpressing cells and control cells. Isolated RNA was then hybridized with the Rat OneArray Plus expression profile chip. The chips were examined by Agilent 0...
December 27, 2017: Nephrology
Stacy A Schaefer, Atsuko Y Higashi, Benjamin Loomis, Thomas Schrepfer, Guoqiang Wan, Gabriel Corfas, Gregory R Dressler, Robert Keith Duncan
Producing hair cells of the inner ear is the major goal of ongoing research that combines advances in developmental and stem cell biology. The recent advent of an inner ear organoid protocol-resulting in three-dimensional stem cell-derived tissues resembling vestibular sensory epithelia-has sparked interest in applications such as regeneration, drug discovery, and disease modeling. In this study, we adapted this protocol for a novel mouse embryonic stem cell line with a fluorescent reporter for Pax2 expression...
February 15, 2018: Stem Cells and Development
Y Song, J Zuo, X Huang, G H Shen, X Y Liu, X Zhang
Objective: To investigate the expressions and clinical significances of paired box gene 2 (Pax2) and cyclin D1 protein in advanced ovarian serous carcinoma. Methods: From January 2003 to December 2013, the pathologic tissues of 202 patients with advanced ovarian serous cancer (Ⅲ-Ⅳ) who underwent initial cytoreductive surgery were collected. The expressions of Pax2 and cyclin D1 protein were detected by immunohistochemistry in tissue microarray. The relationships of their expressions with the clinicopathological features and prognosis of the patients were analyzed...
December 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Salim Megat, Stephanie Shiers, Jamie K Moy, Paulino Barragan-Iglesias, Grishma Pradhan, Rebecca P Seal, Gregory Dussor, Theodore J Price
Dopaminergic modulation of spinal cord plasticity has long been recognized but circuits affected by this system and the precise receptor subtypes involved in this modulation have not been defined. Dopaminergic modulation from the A11 nucleus of the hypothalamus contributes to plasticity in a model of chronic pain called hyperalgesic priming. Here we tested the hypothesis that the key receptor subtype mediating this effect is the D5 receptor (D5R). We find that a spinally-directed lesion of dopaminergic neurons reverses hyperalgesic priming in both sexes and that a D1/D5 antagonist transiently inhibits neuropathic pain...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Annika K Wefers, Christian Haberlandt, Lachezar Surchev, Christian Steinhäuser, Ronald Jabs, Karl Schilling
The cerebellum arguably constitutes one of the best characterized central nervous circuits, and its structure, cellular function, and histogenesis have been described in exceptional quantitative detail. A notable exception to this is the development of its inhibitory interneurons, and in particular the extensive migrations of future basket and stellate cells. Here, we used acute slices from 8-day-old mice to assess the migration of Pax2-EGFP-tagged precursors of these cells en route to the molecular layer during their transit through the nascent cerebellar cortex...
November 17, 2017: Cerebellum
Jun Yang, Du He, Yan Peng, Hongzhen Zhong, Yuhong Deng, Zhonghua Yu, Chengnong Guan, Yufang Zuo, Zumin Xu
Non-small cell lung cancer (NSCLC) is the major cause of deaths among all the cancer types worldwide. Most of the NSCLC is diagnosed at an advanced stage and the 5-year overall survival rate is low. The reason for the low survival rate of patients with NSCLC is mainly due to distant metastasis. Matrine, a traditional Chinese medicine, has been shown a significant anti-proliferation and anti-invasive effect in tumors. However, little is known on the anti-invasive mechanism of matrine in lung cancer. Therefore, we tried to investigate the molecular mechanism of matrine on the invasive ability of NSCLC cells in vitro...
2017: OncoTargets and Therapy
Yujia Lu, Wei Li
E2F3 is a transcription factor that has been shown to be overexpressed in hepatocellular carcinoma (HCC). It is well-known that the E2F3 gene encodes two proteins E2F3a and E2F3b. Therefore, the functions of the two distinct isoforms need to be clarified separately. To characterize the function of E2F3b in HCC, the effects of ectopic expression of E2F3b on cell proliferation, cell cycle, apoptosis and gene expression were investigated. E2F3b promoted G1/S phase transition and markedly increased cell proliferation, but had minor effect on apoptosis...
November 14, 2017: Journal of Cellular Biochemistry
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