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https://www.readbyqxmd.com/read/28892094/deletion-of-pkd1-in-renal-stromal-cells-causes-defects-in-the-renal-stromal-compartment-and-progressive-cystogenesis-in-the-kidney
#1
Xuguang Nie, Lois J Arend
Autosomal dominant polycystic kidney disease (ADPKD), caused by PKD1 and PKD2 gene mutations, is one of the most common genetic diseases, affecting up to 1 in 500 people. Mutations of PKD1 account for over 85% of ADPKD cases. However, mechanisms of disease progression and explanations for the wide range in disease phenotype remain to be elucidated. Moreover, functional roles of PKD1 in the renal stromal compartment are poorly understood. In this work, we tested if Pkd1 is essential for development and maintenance of the renal stromal compartment and if this role contributes to pathogenesis of polycystic kidney disease using a novel tissue-specific knockout mouse model...
September 11, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28701517/mesangial-cell-mammalian-target-of-rapamycin-complex-1-activation-results-in-mesangial-expansion
#2
Kojiro Nagai, Tatsuya Tominaga, Sayo Ueda, Eriko Shibata, Masanori Tamaki, Motokazu Matsuura, Seiji Kishi, Taichi Murakami, Tatsumi Moriya, Hideharu Abe, Toshio Doi
Human glomerular diseases can be caused by several different diseases, many of which include mesangial expansion and/or proliferation followed by glomerulosclerosis. However, molecular mechanisms underlying the pathologic mesangial changes remain poorly understood. Here, we investigated the role of the mammalian target of rapamycin complex 1 (mTORC1)-S6 kinase pathway in mesangial expansion and/or proliferation by ablating an upstream negative regulator, tuberous sclerosis complex 1 (TSC1), using tamoxifen-induced Foxd1-Cre mice [Foxd1ER(+) TSC1 mice]...
July 12, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28665931/foxd1-is-an-upstream-regulator-of-the-renin-angiotensin-system-during-metanephric-kidney-development
#3
Renfang Song, Maria Luisa S Sequeira Lopez, Ihor V Yosypiv
BackgroundWe tested the hypothesis that Foxd1, a transcription factor essential for normal kidney development, is an upstream regulator of the renin-angiotensin system (RAS) during ureteric bud (UB)-branching morphogenesis.MethodsUB branching, RAS gene, and protein expression were studied in embryonic mouse kidneys. RAS mRNA expression was studied in mesenchymal MK4 cells.ResultsThe number of UB tips was reduced in Foxd1(-/-) compared with that in Foxd1(+/+) metanephroi on embryonic day E12.5 (14±2.1 vs. 28±1...
August 2, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28651950/the-loss-of-kr%C3%A3-ppel-like-factor-15-in-foxd1-stromal-cells-exacerbates-kidney-fibrosis
#4
Xiangchen Gu, Sandeep K Mallipattu, Yiqing Guo, Monica P Revelo, Jesse Pace, Timothy Miller, Xiang Gao, Mukesh K Jain, Agnieszka B Bialkowska, Vincent W Yang, John C He, Changlin Mei
Large epidemiological studies clearly demonstrate that multiple episodes of acute kidney injury contribute to the development and progression of kidney fibrosis. Although our understanding of kidney fibrosis has improved in the past two decades, we have limited therapeutic strategies to halt its progression. Myofibroblast differentiation and proliferation remain critical to the progression of kidney fibrosis. Although canonical Wnt signaling can trigger the activation of myofibroblasts in the kidney, mediators of Wnt inhibition in the resident progenitor cells are unclear...
June 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28621426/foxd1-protein-interacts-with-wnt-and-bmp-signaling-to-differentially-pattern-mesoderm-and-neural-tissue
#5
Hanna Polevoy, Anastasia Malyarova, Yuri Fonar, Sara Elias, Dale Frank
The foxd1 gene (previously known as Brain Factor 2/BF2) is expressed during early Xenopus laevis development. At gastrula stages, foxd1 is expressed in dorsal mesoderm regions fated for muscle and notochord, while at neurula stages, foxd1 is expressed in the forebrain region. Previous studies in the neural plate showed that FoxD1 protein acts as transcriptional repressor downstream of BMP antagonism, neuralizing the embryo to control anterior neural cell fates. FoxD1 mesoderm function was not rigorously analyzed, but ectopic FoxD1 levels increased muscle marker expression in embryos...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28539333/endothelial-markers-expressing-stromal-cells-are-critical-for-kidney-formation
#6
Elina Mukherjee, Katherine Virginia Maringer, Emily Papke, Daniel S Bushnell, Caitlin M Schaefer, Rafael Kramann, Jacqueline Ho, Benjamin D Humphreys, Carlton M Bates, Sunder Sims-Lucas
Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins and roles of developing renal endothelial cells in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28535371/repression-of-interstitial-identity-in-nephron-progenitor-cells-by-pax2-establishes-the-nephron-interstitium-boundary-during-kidney-development
#7
Natalie Naiman, Kaoru Fujioka, Mari Fujino, M Todd Valerius, S Steven Potter, Andrew P McMahon, Akio Kobayashi
The kidney contains the functional units, the nephrons, surrounded by the renal interstitium. Previously we discovered that, once Six2-expressing nephron progenitor cells and Foxd1-expressing renal interstitial progenitor cells form at the onset of kidney development, descendant cells from these populations contribute exclusively to the main body of nephrons and renal interstitial tissues, respectively, indicating a lineage boundary between the nephron and renal interstitial compartments. Currently it is unclear how lineages are regulated during kidney organogenesis...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535367/pax2-a-keep-to-the-path-sign-on-waddington-s-epigenetic-landscape
#8
Jamie Davies
Developing kidneys have Foxd1(+) stromogenic stem cells and [Six2(+), Pax2(+)] nephrogenic stem cells. In this issue of Developmental Cell, Naiman et al. (2017) show that targeted Pax2 deletion converts nephrogenic cells to the stromogenic path, suggesting that Pax2 normally represses an otherwise inevitable transition between sister lineages.
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28527294/activation-of-hypoxia-signaling-in-stromal-progenitors-impairs-kidney-development
#9
Katharina Gerl, Dominik Steppan, Michaela Fuchs, Charlotte Wagner, Carsten Willam, Armin Kurtz, Birgül Kurt
Intrauterine hypoxia is a reason for impaired kidney development. The cellular and molecular pathways along which hypoxia exerts effects on nephrogenesis are not well understood. They are likely triggered by hypoxia-inducible transcription factors (HIFs), and their effects appear to be dependent on the cell compartment contributing to kidney formation. In this study, we investigated the effects of HIF activation in the developing renal stroma, which also essentially modulates nephron development from the metanephric mesenchyme...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28439006/murine-model-indicates-22q11-2-signaling-adaptor-crkl-is-a-dosage-sensitive-regulator-of-genitourinary-development
#10
Meade Haller, Qianxing Mo, Akira Imamoto, Dolores J Lamb
The spectrum of congenital anomalies affecting either the upper tract (kidneys and ureters) or lower tract (reproductive organs) of the genitourinary (GU) system are fundamentally linked by the developmental origin of multiple GU tissues, including the kidneys, gonads, and reproductive ductal systems: the intermediate mesoderm. Although ∼31% of DiGeorge/del22q11.2 syndrome patients exhibit GU defects, little focus has been placed on the molecular etiology of GU defects in this syndrome. Among del22q11.2 patients exhibiting GU anomalies, we have mapped the smallest relevant region to only five genes, including CRKLCRKL encodes a src-homology adaptor protein implicated in mediating tyrosine kinase signaling, and is expressed in the developing GU-tract in mice and humans...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286175/cilia-dependent-gli-processing-in-neural-crest-cells-is-required-for-tongue-development
#11
Grethel Millington, Kelsey H Elliott, Ya-Ting Chang, Ching-Fang Chang, Andrzej Dlugosz, Samantha A Brugmann
Ciliopathies are a class of diseases caused by the loss of a ubiquitous, microtubule-based organelle called a primary cilium. Ciliopathies commonly result in defective development of the craniofacial complex, causing midfacial defects, craniosynostosis, micrognathia and aglossia. Herein, we explored how the conditional loss of primary cilia on neural crest cells (Kif3a(f/f);Wnt1-Cre) generated aglossia. On a cellular level, our data revealed that aglossia in Kif3a(f/f);Wnt1-Cre embryos was due to a loss of mesoderm-derived muscle precursors migrating into and surviving in the tongue anlage...
April 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28075458/silencing-of-forkhead-box-d1-inhibits-proliferation-and-migration-in-glioma-cells
#12
Yuan-Feng Gao, Tao Zhu, Xiao-Yuan Mao, Chen-Xue Mao, Ling Li, Ji-Ye Yin, Hong-Hao Zhou, Zhao-Qian Liu
Despite the extensive role of Forkhead box transcription factors in the development and progression of various cancers, little is known about their role in glioma. We examined the expression and function of Forkhead box D1 (FOXD1) in glioma cell behavior and found that FOXD1 was upregulated and directly correlated with the glioma grade. Data analysis also revealed significant differences in FOXD1 expression for both gene expression profiles (GSE4290 and GSE7696) and the TCGA datasets. Additionally, decreased FOXD1 expression in U251 and U87 glioma cells caused a delay in cell growth and a disruption in colony formation...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27805902/association-of-foxd1-variants-with-adverse-pregnancy-outcomes-in-mice-and-humans
#13
Paul Laissue, Besma Lakhal, Magalie Vatin, Frank Batista, Gaëtan Burgio, Eric Mercier, Esther Dos Santos, Christophe Buffat, Diana Carolina Sierra-Diaz, Gilles Renault, Xavier Montagutelli, Jane Salmon, Philippe Monget, Reiner A Veitia, Céline Méhats, Marc Fellous, Jean-Christophe Gris, Julie Cocquet, Daniel Vaiman
Recurrent spontaneous abortion (RSA) is a common cause of infertility, but previous attempts at identifying RSA causative genes have been relatively unsuccessful. Such failure to describe RSA aetiological genes might be explained by the fact that reproductive phenotypes should be considered as quantitative traits resulting from the intricate interaction of numerous genetic, epigenetic and environmental factors. Here, we studied an interspecific recombinant congenic strain (IRCS) of Mus musculus from the C57BL6/J strain of mice harbouring an approximate 5 Mb DNA fragment from chromosome 13 from Mus spretus mice (66H-MMU13 strain), with a high rate of embryonic resorption (ER)...
October 2016: Open Biology
https://www.readbyqxmd.com/read/27779900/ablation-of-pericyte-like-cells-in-lungs-by-oropharyngeal-aspiration-of-diphtheria-toxin
#14
Chi F Hung, Yu-Hua Chow, W Conrad Liles, William A Altemeier, Lynn M Schnapp
We demonstrated previously that FoxD1-derived cells in the lung are enriched in pericyte-like cells in mouse lung. These cells express the common pericyte markers and are located adjacent to endothelial cells. In this study, we demonstrate the feasibility of administering diphtheria toxin (DT) by oropharyngeal aspiration as an approach to ablating FoxD1-derived cells. We crossed mice expressing Cre-recombinase under the FoxD1 promoter to Rosa26-loxP-STOP-loxP-iDTR mice and generated a bitransgenic line (FoxD1-Cre;Rs26-iDTR) in which FoxD1-derived cells heritably express simian or human diphtheria toxin receptor and are sensitive to DT...
February 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27582005/impairment-of-wnt11-function-leads-to-kidney-tubular-abnormalities-and-secondary-glomerular-cystogenesis
#15
Irina I Nagy, Qi Xu, Florence Naillat, Nsrein Ali, Ilkka Miinalainen, Anatoly Samoylenko, Seppo J Vainio
BACKGROUND: Wnt11 is a member of the Wnt family of secreted signals controlling the early steps in ureteric bud (UB) branching. Due to the reported lethality of Wnt11 knockout embryos in utero, its role in later mammalian kidney organogenesis remains open. The presence of Wnt11 in the emerging tubular system suggests that it may have certain roles later in the development of the epithelial ductal system. RESULTS: The Wnt11 knockout allele was backcrossed with the C57Bl6 strain for several generations to address possible differences in penetrance of the kidney phenotypes...
August 31, 2016: BMC Developmental Biology
https://www.readbyqxmd.com/read/27569208/foxd1-aldh1a3-signaling-is-a-determinant-for-the-self-renewal-and-tumorigenicity-of-mesenchymal-glioma-stem-cells
#16
Peng Cheng, Jia Wang, Indrayani Waghmare, Stefania Sartini, Vito Coviello, Zhuo Zhang, Sung-Hak Kim, Ahmed Mohyeldin, Marat S Pavlyukov, Mutsuko Minata, Claudia L L Valentim, Rishi Raj Chhipa, Krishna P L Bhat, Biplab Dasgupta, Concettina La Motta, Madhuri Kango-Singh, Ichiro Nakano
Glioma stem-like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural GSC subtype...
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27501774/genome-wide-transcriptome-and-binding-sites-analyses-identify-early-fox-expressions-for-enhancing-cardiomyogenesis-efficiency-of-hesc-cultures
#17
Hock Chuan Yeo, Sherwin Ting, Romulo Martin Brena, Geoffrey Koh, Allen Chen, Siew Qi Toh, Yu Ming Lim, Steve Kah Weng Oh, Dong-Yup Lee
The differentiation efficiency of human embryonic stem cells (hESCs) into heart muscle cells (cardiomyocytes) is highly sensitive to culture conditions. To elucidate the regulatory mechanisms involved, we investigated hESCs grown on three distinct culture platforms: feeder-free Matrigel, mouse embryonic fibroblast feeders, and Matrigel replated on feeders. At the outset, we profiled and quantified their differentiation efficiency, transcriptome, transcription factor binding sites and DNA-methylation. Subsequent genome-wide analyses allowed us to reconstruct the relevant interactome, thereby forming the regulatory basis for implicating the contrasting differentiation efficiency of the culture conditions...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27458175/integrative-analysis-of-microarray-data-to-reveal-regulation-patterns-in-the-pathogenesis-of-hepatocellular-carcinoma
#18
Juan Chen, Zhenwen Qian, Fengling Li, Jinzhi Li, Yi Lu
Background/Aims: The integration of multiple profiling data and the construction of a transcriptional regulatory network may provide additional insights into the molecular mechanisms of hepatocellular carcinoma (HCC). The present study was conducted to investigate the deregulation of genes and the transcriptional regulatory network in HCC. Methods: An integrated analysis of HCC gene expression datasets was performed in Gene Expression Omnibus. Functional annotation of the differentially expression genes (DEGs) was conducted...
January 15, 2017: Gut and Liver
https://www.readbyqxmd.com/read/27403158/screening-driving-transcription-factors-in-the-processing-of-gastric-cancer
#19
Guangzhong Xu, Kai Li, Nengwei Zhang, Bin Zhu, Guosheng Feng
Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer. Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed. Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs...
2016: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/27335372/maintenance-of-vascular-integrity-by-pericytes-is-essential-for-normal-kidney-function
#20
Dario R Lemos, Graham Marsh, Angela Huang, Gabriela Campanholle, Takahide Aburatani, Lan Dang, Ivan Gomez, Ken Fisher, Giovanni Ligresti, Janos Peti-Peterdi, Jeremy S Duffield
Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice...
December 1, 2016: American Journal of Physiology. Renal Physiology
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