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Aikaterini Gravia, Vasiliki Chondrou, Alexandra Kolliopoulou, Alexandra Kourakli, Anne John, Argyris Symeonidis, Bassam R Ali, Argyro Sgourou, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
AIMS: Hemoglobinopathies, particularly β-thalassemia and sickle cell disease, are characterized by great phenotypic variability in terms of disease severity, while notable differences have been observed in hydroxyurea treatment efficacy. In both cases, the observed phenotypic diversity is mostly dependent on the elevated fetal hemoglobin levels, resulting from the persistent fetal globin gene expression in the adult erythroid stage orchestrated by intricate mechanisms that still remain only partly understood...
October 21, 2016: Pharmacogenomics
Malek Kammoun, Philippe Pouletaut, Francis Canon, Malayannan Subramaniam, John R Hawse, Muriel Vayssade, Sabine F Bensamoun
As transforming growth factor (TGF)-β inducible early gene-1 is highly expressed in skeletal muscle, the effect of TIEG1 gene deletion on the passive mechanical properties of slow and fast twitch muscle fibers was analyzed. Twenty five muscle fibers were harvested from soleus (Sol) and extensor digitorum longus (EDL) muscles from TIEG1-/- (N = 5) and control (N = 5) mice. Mechanical tests were performed on fibers and the dynamic and static stresses were measured. A viscoelastic Hill model of 3rd order was used to fit the experimental relaxation test data...
2016: PloS One
Liang-Ti Huang, Hsuen-Wen Chang, Min-Ju Wu, Yong-Tzuo Lai, Wen-Chi Wu, Winston C Y Yu, Vincent H S Chang
KLF10 is a transforming growth factor (TGF)-β/Smad downstream regulated gene. KLF10 binds to the promoter of target genes and mimics the effects of TGF-β as a transcriptional factor. In our laboratory, we noted that Klf10 deficiency in mice is associated with significant inflammation of the lungs. However, the precise mechanism of this association remains unknown. We previously identified NPRA as a target gene potentially regulated by KLF10 through direct binding; NPRA knockout have known that prevented lung inflammation in a mouse model of allergic asthma...
October 2016: International Journal of Biochemistry & Cell Biology
Abigail A Delaney, Zaraq Khan, Ye Zheng, Luiz F Correa, Valentina Zanfagnin, Chandra C Shenoy, John K Schoolmeester, Abdulrahman M Saadalla, Sherif El-Nashar, Abimbola O Famuyide, Malayannan Subramaniam, John R Hawse, Khashayarsha Khazaie, Gaurang S Daftary
Endometriosis is a highly prevalent, chronic, heterogeneous, fibro-inflammatory disease that remains recalcitrant to conventional therapy. We previously showed that loss of KLF11, a transcription factor implicated in uterine disease, results in progression of endometriosis. Despite extensive homology, co-expression, and human disease association, loss of the paralog Klf10 causes a unique inflammatory, cystic endometriosis phenotype in contrast to fibrotic progression seen with loss of Klf11. We identify here for the first time a novel role for KLF10 in endometriosis...
September 2016: Biology of Reproduction
Prem Swaroop Yadav, Mohd Parvez Khan, Paritosh Prashar, Shivali Duggal, Srikanta Kumar Rath, Naibedya Chattopadhyay, Amitabha Bandyopadhyay
Adipogenesis, chondrogenesis and osteogenesis are BMP signaling dependent differentiation processes. However, the molecular networks operating downstream of BMP signaling to bring about these distinct fates are yet to be fully elucidated. We have developed a novel Bone Marrow Stromal Cell (BMSC) derived mouse cell line as a powerful in vitro platform to conduct such experiments. This cell line is a derivative of BMSCs isolated from a tamoxifen inducible Bmp2 and Bmp4 double conditional knock-out mouse strain...
October 2016: Bone
Lili Zheng, Lingling Chen, Xuan Zhang, Jingfen Zhan, Jie Chen
Ovarian cancer is one of the greatest causes of cancer death in women. The association of TMEM49 and ovarian cancer is poorly defined. Here, we reported that TMEM49 was significantly increased in ovarian tumor tissues compared to ovarian normal tissues. Furthermore, down-regulation of TMEM49 through RNA interference inhibited cell proliferation and arrested G1/S transition in two ovarian cancer cell lines, OVCAR3 and A2780. More importantly, TMEM49 silencing induced cell apoptosis. Additionally, down-regulation of TMEM49 in ovarian cancer notably repressed cell invasion and adhesion...
May 2016: Molecular and Cellular Biochemistry
Xiaoyin Ma, Xiaodong Jiao, Zhiwei Ma, J Fielding Hejtmancik
CRYAA plays critical functional roles in lens transparency and opacity, and polymorphisms near CRYAA have been associated with age-related cataract (ARC). This study examines polymorphisms in the CRYAA promoter region for association with ARC and elucidates the mechanisms of this association. Three SNPs nominally associated with ARC were identified in the promoter region of CRYAA: rs3761382 (P = 0.06, OR (Odds ratio) = 1.5), rs13053109 (P = 0.04, OR = 1.6), rs7278468 (P = 0.007, OR = 0...
2016: Scientific Reports
Hyojung Jeon, Tsuyoshi Waku, Takuya Azami, Le Tran Phuc Khoa, Jun Yanagisawa, Satoru Takahashi, Masatsugu Ema
Pluripotency is maintained in mouse embryonic stem (ES) cells and is induced from somatic cells by the activation of appropriate transcriptional regulatory networks. Krüppel-like factor gene family members, such as Klf2, Klf4 and Klf5, have important roles in maintaining the undifferentiated state of mouse ES cells as well as in cellular reprogramming, yet it is not known whether other Klf family members exert self-renewal and reprogramming functions when overexpressed. In this study, we examined whether overexpression of any representative Klf family member, such as Klf1-Klf10, would be sufficient for the self-renewal of mouse ES cells...
2016: PloS One
Heather S L Jim, Hui-Yi Lin, Jonathan P Tyrer, Kate Lawrenson, Joe Dennis, Ganna Chornokur, Zhihua Chen, Ann Y Chen, Jennifer Permuth-Wey, Katja Kh Aben, Hoda Anton-Culver, Natalia Antonenkova, Fiona Bruinsma, Elisa V Bandera, Yukie T Bean, Matthias W Beckmann, Maria Bisogna, Line Bjorge, Natalia Bogdanova, Louise A Brinton, Angela Brooks-Wilson, Clareann H Bunker, Ralf Butzow, Ian G Campbell, Karen Carty, Jenny Chang-Claude, Linda S Cook, Daniel W Cramer, Julie M Cunningham, Cezary Cybulski, Agnieszka Dansonka-Mieszkowska, Andreas du Bois, Evelyn Despierre, Weiva Sieh, Jennifer A Doherty, Thilo Dörk, Matthias Dürst, Douglas F Easton, Diana M Eccles, Robert P Edwards, Arif B Ekici, Peter A Fasching, Brooke L Fridley, Yu-Tang Gao, Aleksandra Gentry-Maharaj, Graham G Giles, Rosalind Glasspool, Marc T Goodman, Jacek Gronwald, Philipp Harter, Hanis N Hasmad, Alexander Hein, Florian Heitz, Michelle A T Hildebrandt, Peter Hillemanns, Claus K Hogdall, Estrid Hogdall, Satoyo Hosono, Edwin S Iversen, Anna Jakubowska, Allan Jensen, Bu-Tian Ji, Beth Y Karlan, Melissa Kellar, Lambertus A Kiemeney, Camilla Krakstad, Susanne K Kjaer, Jolanta Kupryjanczyk, Robert A Vierkant, Diether Lambrechts, Sandrina Lambrechts, Nhu D Le, Alice W Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas A Levine, Dong Liang, Boon Kiong Lim, Jolanta Lissowska, Karen Lu, Jan Lubinski, Lene Lundvall, Leon F A G Massuger, Keitaro Matsuo, Valerie McGuire, John R McLaughlin, Ian McNeish, Usha Menon, Roger L Milne, Francesmary Modugno, Lotte Thomsen, Kirsten B Moysich, Roberta B Ness, Heli Nevanlinna, Ursula Eilber, Kunle Odunsi, Sara H Olson, Irene Orlow, Sandra Orsulic, Rachel Palmieri Weber, James Paul, Celeste L Pearce, Tanja Pejovic, Liisa M Pelttari, Malcolm C Pike, Elizabeth M Poole, Eva Schernhammer, Harvey A Risch, Barry Rosen, Mary Anne Rossing, Joseph H Rothstein, Anja Rudolph, Ingo B Runnebaum, Iwona K Rzepecka, Helga B Salvesen, Ira Schwaab, Xiao-Ou Shu, Yurii B Shvetsov, Nadeem Siddiqui, Honglin Song, Melissa C Southey, Beata Spiewankiewicz, Lara Sucheston-Campbell, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Ingvild L Tangen, Shelley S Tworoger, Anne M van Altena, Ignace Vergote, Christine S Walsh, Shan Wang-Gohrke, Nicolas Wentzensen, Alice S Whittemore, Kristine G Wicklund, Lynne R Wilkens, Anna H Wu, Xifeng Wu, Yin-Ling Woo, Hannah Yang, Wei Zheng, Argyrios Ziogas, Ernest Amankwah, Andrew Berchuck, Joellen M Schildkraut, Linda E Kelemen, Susan J Ramus, Alvaro N A Monteiro, Ellen L Goode, Steven A Narod, Simon A Gayther, Paul D P Pharoah, Thomas A Sellers, Catherine M Phelan
Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness...
2015: Journal of Genetics and Genome Research
Malayannan Subramaniam, Kevin S Pitel, Sarah G Withers, Hicham Drissi, John R Hawse
Deletion of TIEG1/KLF10 in mice results in an osteopenic skeletal phenotype with significant decreases in both bone mineral density and content throughout the skeleton. Calvarial osteoblasts isolated from TIEG1 knockout (KO) mice display numerous changes in gene expression and exhibit significant delays in their mineralization rates relative to wild-type (WT) controls. Here, we demonstrate that loss of TIEG1 expression in osteoblasts results in decreased levels of Osterix mRNA. Suppression of TIEG1 expression in WT osteoblasts leads to decreased Osterix expression while restoration of TIEG1 expression in TIEG1 KO osteoblasts results in increased levels of Osterix...
February 12, 2016: Biochemical and Biophysical Research Communications
Min-Chih Cheng, Shih-Hsin Hsu, Chia-Hsiang Chen
Methamphetamine (METH) is a highly addictive psychostimulant that may cause long-lasting synaptic dysfunction and abnormal gene expression. We aimed to explore the differential expression of synaptic plasticity genes in chronic METH-treated mouse brain. We used the RT(2) Profiler PCR Array and the real-time quantitative PCR to characterize differentially expressed synaptic plasticity genes in the frontal cortex and the hippocampus of chronic METH-treated mice compared with normal saline-treated mice. We further used pyrosequencing to assess DNA methylation changes in the CpG region of the five immediate early genes (IEGs) in chronic METH-treated mouse brain...
December 10, 2015: Brain Research
Konstantinos A Papadakis, James Krempski, Phyllis Svingen, Yuning Xiong, Olga F Sarmento, Gwen A Lomberk, Raul A Urrutia, William A Faubion
Krüppel-like factor (KLF)-10 is an important transcriptional regulator of TGF-β1 signaling in both CD8(+) and CD4(+) T lymphocytes. In the present study, we demonstrate a novel role for KLF10 in the regulation of TGFβRII expression with functional relevance in macrophage differentiation and activation. We first show that transfer of KLF10(-/-) bone marrow-derived macrophages into wild-type (WT) mice leads to exacerbation of experimental colitis. At the cell biological level, using two phenotypic strategies, we show that KLF10-deficient mice have an altered colonic macrophage phenotype with higher frequency of proinflammatory LyC6(+)MHCII(+) cells and a reciprocal decrease of the anti-inflammatory LyC6(-)MHCII(+) subset...
December 1, 2015: American Journal of Physiology. Gastrointestinal and Liver Physiology
Zhuo Chen, Wentong Li, Han Wang, Chunyan Wan, Daoshu Luo, Shuli Deng, Hui Chen, Shuo Chen
Klf10, a member of the Krüppel-like family of transcription factors, is critical for osteoblast differentiation, bone formation and mineralization. However, whether Klf10 is involved in odontoblastic differentiation and tooth development has not been determined. In this study, we investigate the expression patterns of Klf10 during murine tooth development in vivo and its role in odontoblastic differentiation in vitro. Klf10 protein was expressed in the enamel organ and the underlying mesenchyme, ameloblasts and odontoblasts at early and later stages of murine molar formation...
February 2016: Cell and Tissue Research
Jimin Pei, Nick V Grishin
Specificity proteins (SPs) and Krüppel-Like Factors (KLFs) are C2H2-type zinc finger transcription factors that play essential roles in differentiation, development, proliferation and cell death. SP/KLF proteins, similarly to Wilms tumor protein 1 (WT1), Early Growth Response (EGR), Huckebein, and Klumpfuss, prefer to bind GC-rich sequences such as GC-box and CACCC-box (GT-box). We searched various genomes and transcriptomes of metazoans and single-cell holozoans for members of these families. Seven groups of KLFs (KLFA-G) and three groups of SPs (SPA-C) were identified in the three lineages of Bilateria (Deuterostomia, Ecdysozoa, and Lophotrochozoa)...
November 15, 2015: Gene
Ming Li, Jia-Nee Foo, Jin-Quan Wang, Hui-Qi Low, Xue-Qing Tang, Kai-Yee Toh, Pei-Ran Yin, Chiea-Chuen Khor, Yu-Fen Goh, Ishak D Irwan, Ri-Cong Xu, Anand K Andiappan, Jin-Xin Bei, Olaf Rotzschke, Meng-Hua Chen, Ching-Yu Cheng, Liang-Dan Sun, Geng-Ru Jiang, Tien-Yin Wong, Hong-Li Lin, Tin Aung, Yun-Hua Liao, Seang-Mei Saw, Kun Ye, Richard P Ebstein, Qin-Kai Chen, Wei Shi, Soo-Hong Chew, Jian Chen, Fu-Ren Zhang, Sheng-Ping Li, Gang Xu, E Shyong Tai, Li Wang, Nan Chen, Xue-Jun Zhang, Yi-Xin Zeng, Hong Zhang, Zhi-Hong Liu, Xue-Qing Yu, Jian-Jun Liu
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1...
2015: Nature Communications
Ching-Hui Lin, Shu-Yu Lin, Hsuen-Wen Chang, Li-Jung Ko, Yan-Shen Tseng, Vincent H S Chang, Winston C Y Yu
Downregulation of multiple cell cycle-regulatory molecules is a dominant event in TGF-β1-mediated growth inhibition of human carcinoma cells. It is known that KLF10 mimics the anti-proliferative and apoptotic effects that TGF-β1 has on epithelial cell growth and the growth of various tumor cells; based on these findings it is considered as a tumor suppressor. KLF10 protein expression is tightly associated with cell cycle-dependent events. However, the regulatory mechanism and its biological meaning have not been identified...
May 2015: Biochimica et Biophysica Acta
Seung-Ho Heo, Eui-Suk Jeong, Kyoung-Sun Lee, Jin-Hee Seo, Woon-Kyu Lee, Yang-Kyu Choi
Liver cancer is the third most common cancer, and the incidence as well as the mortality rate of liver cancer are on the increase. There are many signaling pathways that are involved in hepatic tumorigenesis. One of these pathways, the transforming growth factor-β (TGF-β)/Smad pathway with KLF10, has been reported to suppress cellular proliferation in most cases. However, the actual functions of KLF10 in various pathophysiological conditions are still fragmentary and unclear. In the present study, the practical role of KLF10 in DEN-induced hepatic carcinogenesis, was elucidated using KLF10 null mice...
April 2015: Oncology Reports
Santosh A Khedkar, Xinghui Sun, Alan C Rigby, Mark W Feinberg
The Krüppel-like family of transcription factors (KLFs) constitute a subfamily of C2H2-type zinc finger proteins with distinct cell-type expression patterns and regulate functional aspects of cell growth and differentiation, activation, or development. KLF10 has been previously shown to critically regulate the acquisition of CD4+CD25+ T regulatory cell differentiation and function, an effect important to the maintenance of self-tolerance, immune suppression, and tumor immunosurveillance. To date, there are no selective pharmacological inhibitors to KLF10...
February 12, 2015: Journal of Medicinal Chemistry
Min-Ju Wu, Wen-Chi Wu, Hsuen-Wen Chang, Yong-Tzuo Lai, Ching-Hui Lin, Winston C Y Yu, Vincent H S Chang
TGF-β plays a significant role in regulating pancreas islet function and maintaining their mass. KLF10, a TGF-β downstream gene, belongs to a group of Krüppel-like transcription factors that bind to the promoters of target genes and produce effects that mimic TGF-β as a tumor suppressor. Using ChIP-chip screening, SEI-1 was identified as a target gene that may be regulated by KLF10. We conducted a series of assays to verify the presence of unknown regulation events between SEI-1 and KLF10. These showed that KLF10 transcriptionally activates the SEI-1 promoter and, furthermore, induces SEI-1 protein expression in pancreatic carcinoma cells...
March 2015: International Journal of Biochemistry & Cell Biology
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