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Chengji Cui, Yabin Cui, Yanyan Fu, Sichao Ma, Shoulin Zhang
The current study aimed to identify therapeutic gene and microRNA (miRNA) biomarkers for diabetic kidney disease (DKD). The public expression profile GSE30122 was used. Following data preprocessing, the limma package was used to select differentially-expressed genes (DEGs) in DKD glomeruli samples and tubuli samples and they were compared with corresponding controls. Then overlapping DEGs in glomeruli and tubuli were identified and enriched analysis was performed. In addition, protein‑protein interaction (PPI) network analysis as well as sub‑network analysis was conducted...
February 2018: Molecular Medicine Reports
Wei Jiang, Mengping Wei, Mengna Liu, Yunlong Pan, Dong Cao, Xiaofei Yang, Chen Zhang
The proper formation of synapses-specialized unitary structures formed between two neurons-is critical to mediating information flow in the brain. Synaptic cell adhesion molecules (CAMs) are thought to participate in the initiation of the synapse formation process. However, in vivo functional analysis demonstrates that most well known synaptic CAMs regulate synaptic maturation and plasticity rather than synapse formation, suggesting that either CAMs work synergistically in the process of forming synapses or more CAMs remain to be found...
October 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Fei Ming, Qianqiang Sun
Protein tyrosine phosphatase receptor‑type O (PTPRO), a member of the PTP family, has been frequently reported as potential tumor suppressor in many types of cancer. However, the exact function of PTPRO in lung squamous cell carcinoma (LSCC) remains unclear. Bisulfite sequencing and methylation specific polymerase chain reaction (PCR) were used to identify the methylation status of PTPRO in LSCC cells, and quantitative methylation specific PCR was used to evaluate the methylation levels of PTPRO in LSCC patients...
July 2017: Molecular Medicine Reports
Caihong Liang, Xiaochen Wang, Jianping Hu, Xiaoqing Lian, Tiantian Zhu, Hui Zhang, Ning Gu, Jun Li
BACKGROUND/AIMS: Critical roles of phosphatase receptor type O (PTPRO) and toll-like receptor 4 (TLR4) have been implicated in inflammation. However, little is known about their functional effects on atherosclerosis (AS). We aim to study their potential function in AS. METHODS: An oxidized low-density lipoprotein (ox-LDL) induced AS model constructed with PTPRO over-expressing RAW264.7 cells and PTPRO knockout macrophages. Cell apoptosis was assayed by flow cytometry and fatty accumulation was evaluated by oil red staining...
2017: Cellular Physiology and Biochemistry
Javier U Chicote, Rob DeSalle, Antonio García-España
Subtype R3 phosphotyrosine phosphatase receptors (R3 RPTPs) are single-spanning membrane proteins characterized by a unique modular composition of extracellular fibronectin repeats and a single cytoplasmatic protein tyrosine phosphatase (PTP) domain. Vertebrate R3 RPTPs consist of five members: PTPRB, PTPRJ, PTPRH and PTPRO, which dephosphorylate tyrosine residues, and PTPRQ, which dephosphorylates phophoinositides. R3 RPTPs are considered novel therapeutic targets in several pathologies such as ear diseases, nephrotic syndromes and cancer...
2017: PloS One
K S Madill-Thomsen, R C Wiggins, F Eskandary, G A Böhmig, P F Halloran
Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e...
August 2017: American Journal of Transplantation
Josiah E Radder, Yingze Zhang, Alyssa D Gregory, Shibing Yu, Neil J Kelly, Joseph K Leader, Naftali Kaminski, Frank C Sciurba, Steven D Shapiro
RATIONALE: Genetic association studies in chronic obstructive pulmonary disease have primarily tested for association with common variants, the results of which explain only a portion of disease heritability. Because rare variation is also likely to contribute to susceptibility, we used whole-genome sequencing of subjects with clinically extreme phenotypes to identify genomic regions enriched for rare variation contributing to chronic obstructive pulmonary disease susceptibility. OBJECTIVES: To identify regions of rare genetic variation contributing to emphysema with severe airflow obstruction...
July 15, 2017: American Journal of Respiratory and Critical Care Medicine
Michael J Randles, Sophie Collinson, Tobias Starborg, Aleksandr Mironov, Mira Krendel, Eva Königshausen, Lorenz Sellin, Ian S D Roberts, Karl E Kadler, Jeffrey H Miner, Rachel Lennon
Glomeruli are highly sophisticated filters and glomerular disease is the leading cause of kidney failure. Morphological change in glomerular podocytes and the underlying basement membrane are frequently observed in disease, irrespective of the underlying molecular etiology. Standard electron microscopy techniques have enabled the identification and classification of glomerular diseases based on two-dimensional information, however complex three-dimensional ultrastructural relationships between cells and their extracellular matrix cannot be easily resolved with this approach...
October 11, 2016: Scientific Reports
H Dong, L Ma, J Gan, W Lin, C Chen, Z Yao, L Du, L Zheng, C Ke, X Huang, H Song, R Kumar, S C Yeung, H Zhang
The plasma membrane-associated tyrosine phosphatase PTPRO is frequently transcriptionally repressed in cancers and signifies poor prognosis of breast cancer patients. In this study, deletion of Ptpro in MMTV-Erbb2 transgenic mice dramatically shortened the mammary tumor latency and accelerated tumor growth due to loss of Ptpro within the breast cancer cells but not in surrounding tissue as confirmed by hetero-transplantation studies. Both in vitro and in vivo data demonstrated that the phosphatase activity was required for the inactivation of ERBB2 and its downstream signaling...
January 19, 2017: Oncogene
L Ghisdal, C Baron, Y Lebranchu, O Viklický, A Konarikova, M Naesens, D Kuypers, M Dinic, E Alamartine, G Touchard, T Antoine, M Essig, J P Rerolle, P Merville, J L Taupin, Y Le Meur, A Grall-Jezequel, F Glowacki, C Noël, C Legendre, D Anglicheau, N Broeders, W Coppieters, E Docampo, M Georges, Z Ajarchouh, A Massart, J Racapé, D Abramowicz, M Abramowicz
Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort...
January 2017: American Journal of Transplantation
Man-Man Kang, Shun-Lin Shan, Xu-Yang Wen, Hu-Sheng Shan, Zheng-Jun Wang
Tyrosine phosphorylation plays an important role in regulating human physiological and pathological processes. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinated regulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealed PTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions. Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identified to have some roles in tumor development...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Xiaochen Wang, Shushan Yan, Donghua Xu, Jun Li, Yu Xie, Jiajie Hou, Runqiu Jiang, Chuanyong Zhang, Beicheng Sun
BACKGROUND/AIMS: Critical roles of PTPRO and TLR4 have been implicated in hepatocellular carcinoma. However, little is known about their modifying effects on inflammation-related diseases in liver, particularly fulminant hepatitis (FH). We aim to investigate the potential role of PTPRO and its interaction with TLR4 in LPS/D-GaIN induced FH. METHODS: A LPS/D-GaIN induced mouse FH model was used. RAW264.7 cells were transfected with PTPRO over-expressed lentiviral plasmids for further investigation...
2015: Cellular Physiology and Biochemistry
Jiajie Hou, Lei Deng, Han Zhuo, Zhe Lin, Yun Chen, Runqiu Jiang, Dianyu Chen, Xudong Zhang, Xingxu Huang, Beicheng Sun
Intratumoral T cells play a central role in anti-tumor immunity, and the balance between T effector cells (Teff) and regulatory T cells (Treg) affects the prognosis of cancer patients. However, educated by tumor microenvironment, T cells frequently fail in their responsibility. In this study, we aimed to investigate the role of truncated isoform of protein tyrosine phosphatase receptor-type O (PTPROt) in T cell-mediated anti-tumor immunity. We recruited 70 hepatocellular carcinoma (HCC) patients and 30 healthy volunteers for clinical investigation, and analyzed cellular tumor immunity by using ptpro(-/-) C57BL/6 mice and NOD/SCID mice...
August 2015: Journal of Molecular Cell Biology
Takafumi Shintani, Satoru Higashi, Yasushi Takeuchi, Eugenio Gaudio, Francesco Trapasso, Alfredo Fusco, Masaharu Noda
The autophosphorylation of specific tyrosine residues occurs in the cytoplasmic region of the insulin receptor (IR) upon insulin binding, and this in turn initiates signal transduction. The R3 subfamily (Ptprb, Ptprh, Ptprj and Ptpro) of receptor-like protein tyrosine phosphatases (RPTPs) is characterized by an extracellular region with 6-17 fibronectin type III-like repeats and a cytoplasmic region with a single phosphatase domain. We herein identified the IR as a substrate for R3 RPTPs by using the substrate-trapping mutants of R3 RPTPs...
September 2015: Journal of Biochemistry
Maciej Tomaszewski, James Eales, Matthew Denniff, Stephen Myers, Guat Siew Chew, Christopher P Nelson, Paraskevi Christofidou, Aishwarya Desai, Cara Büsst, Lukasz Wojnar, Katarzyna Musialik, Jacek Jozwiak, Radoslaw Debiec, Anna F Dominiczak, Gerjan Navis, Wiek H van Gilst, Pim van der Harst, Nilesh J Samani, Stephen Harrap, Pawel Bogdanski, Ewa Zukowska-Szczechowska, Fadi J Charchar
The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P = 9.65 × 10(-5)) and diastolic BP (P = 7.61 × 10(-3)) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9...
December 2015: Journal of the American Society of Nephrology: JASN
Wenjie Zhang, Jiajie Hou, Xiaochen Wang, Runqiu Jiang, Yin Yin, Jie Ji, Lei Deng, Xingxu Huang, Ke Wang, Beicheng Sun
Autophagy plays a critical role in the progression of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Protein tyrosine phosphatase receptor type O (PTPRO) was recently identified as a tumor suppressor, but little is known about its role in NASH. Here, we investigated the role of PTPRO-dependent autophagy in insulin resistance, lipid metabolism, and hepatocarcinogenesis. Wild-type (WT) and ptpro-/- mice were fed a high-fat diet (HFD) for another 16 weeks after diethylnitrosamine (DEN) injection to induce NASH...
April 20, 2015: Oncotarget
Marcus C Hansen, Charlotte G Nyvold, Anne S Roug, Eigil Kjeldsen, Palle Villesen, Line Nederby, Peter Hokland
We describe a comprehensive molecular analysis of a pair of monozygotic twins, who came to our attention when one experienced amaurosis fugax and was diagnosed with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic B-cell chronic lymphocytic leukaemia (B-CLL). Although JAK2-, Twin B was subsequently shown to have a benign monoclonal B-cell lymphocytosis (MBL). Flow cytometric and molecular analyses of the B-cell compartments revealed different immunoglobulin light and heavy chain usage in each twin...
May 2015: British Journal of Haematology
Zhao Liu, Jiajie Hou, Lidong Ren, Jing He, Beicheng Sun, Lu-Zhe Sun, Shui Wang
Protein tyrosine phosphatase receptor type O (PTPRO) has been recognized as a tumor suppressor in various types of cancer cells. However, little attention has been given to the role of PTPRO expression in the tumor microenvironment. We aimed to reveal the role of PTPRO in the breast cancer niche. Py8119 mouse breast cancer cells were implanted orthotopically into female wild-type or ptpro-/- C57Bl/6 mice. We observed that the loss of PTPRO in the tumor niche was correlated with larger tumor volume, more metastases, increased number of circulating tumor cells (CTCs), less apoptosis and reduced necrosis rates in the orthotopic mouse model of breast cancer...
April 2015: Oncology Reports
Xudong Zhang, Zhongming Tan, Youjing Wang, Junwei Tang, Runjiu Jiang, Jiajie Hou, Han Zhuo, Xiaochen Wang, Jie Ji, Xihu Qin, Beicheng Sun
BACKGROUND/AIMS: PTPRO (protein tyrosine phosphatase, receptor type O) is implicated in diverse physiological and pathological processes in cancer and hepatic ischemia/reperfusion injury, although little is known about its role in hepatic fibrosis. METHODS: Here, by using genetically deficient mice, we reported that PTPRO knockout (PTPRO(-/-)) significantly attenuated liver injury, release of inflammatory factors, tissue remodeling, and liver fibrosis in two experimental mouse models of fibrogenesis induced by bile-duct ligation or carbon tetrachloride administration...
2015: Cellular Physiology and Biochemistry
Christina H Nielsen, Agnete Larsen, Anders L Nielsen
Despite increased awareness, maternal cigarette smoking during pregnancy continues to be a common habit causing risk for numerous documented negative health consequences in the exposed children. It has been proposed that epigenetic mechanisms constitute the link between prenatal exposure to maternal cigarette smoking (PEMCS) and the diverse pathologies arising in later life. We here review the current literature, focusing on DNA methylation. Alterations in the global DNA methylation patterns were observed after exposure to maternal smoking during pregnancy in placenta, cord blood and buccal epithelium tissue...
February 2016: Archives of Toxicology
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