- Browse by Author
Browsing by Author "Zhao, Zhenwen"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1(PLOS, 2009-05-29) Li, Hui; Wang, Dongmei; Singh, Lisam Shanjukumar; Berk, Michael; Tan, Haiyan; Zhao, Zhenwen; Steinmetz, Rosemary; Kirmani, Kashif; Wei, Gang; Xu, Yan; Obstetrics and Gynecology, School of MedicineOvarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK) activation and nitric oxide (NO) production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases.Item Autotaxin expression and its connection with the TNF-alpha-NF-κB axis in human hepatocellular carcinoma(BMC, 2010-03-31) Wu, Jian-Min; Xu, Yan; Skill, Nicholas J.; Sheng, Hongmiao; Zhao, Zhenwen; Yu, Menggang; Saxena, Romil; Maluccio, Mary A.; Surgery, School of MedicineBackground Autotaxin (ATX) is an extracellular lysophospholipase D that generates lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Both ATX and LPA have been shown to be involved in many cancers. However, the functional role of ATX and the regulation of ATX expression in human hepatocellular carcinoma (HCC) remain elusive. Results In this study, ATX expression was evaluated in tissues from 38 human HCC and 10 normal control subjects. ATX was detected mainly in tumor cells within tissue sections and its over-expression in HCC was specifically correlated with inflammation and liver cirrhosis. In addition, ATX expression was examined in normal human hepatocytes and liver cancer cell lines. Hepatoma Hep3B and Huh7 cells displayed stronger ATX expression than hepatoblastoma HepG2 cells and normal hepatocytes did. Proinflammtory cytokine tumor necrosis factor alpha (TNF-α) promoted ATX expression and secretion selectively in Hep3B and Huh7 cells, which led to a corresponding increase in lysophospholipase-D activity. Moreover, we explored the mechanism governing the expression of ATX in hepatoma cells and established a critical role of nuclear factor-kappa B (NF-κB) in basal and TNF-α induced ATX expression. Further study showed that secreted enzymatically active ATX stimulated Hep3B cell invasion. Conclusions This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC. Our observation that links the TNF-α/NF-κB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis.Item Loss of FKBP5 Affects Neuron Synaptic Plasticity: An Electrophysiology Insight(Elsevier, 2019-03) Qiu, Bin; Xu, Yuxue; Wang, Jun; Liu, Ming; Dou, Longyu; Deng, Ran; Wang, Chao; Williams, Kent E.; Stewart, Robert B.; Xie, Zhongwen; Ren, Wei; Zhao, Zhenwen; Shou, Weinian; Liang, Tiebing; Yong, Weidong; Medicine, School of MedicineFKBP5 (FKBP51) is a glucocorticoid receptor (GR) binding protein, which acts as a co-chaperone of heat shock protein 90 (HSP90) and negatively regulates GR. Its association with mental disorders has been identified, but its function in disease development is largely unknown. Long-term potentiation (LTP) is a functional measurement of neuronal connection and communication, and is considered one of the major cellular mechanisms that underlies learning and memory, and is disrupted in many mental diseases. In this study, a reduction in LTP in Fkbp5 knockout (KO) mice was observed when compared to WT mice, which correlated with changes to the glutamatergic and GABAergic signaling pathways. The frequency of mEPSCs was decreased in KO hippocampus, indicating a decrease in excitatory synaptic activity. While no differences were found in levels of glutamate between KO and WT, a reduction was observed in the expression of excitatory glutamate receptors (NMDAR1, NMDAR2B and AMPAR), which initiate and maintain LTP. The expression of the inhibitory neurotransmitter GABA was found to be enhanced in Fkbp5 KO hippocampus. Further investigation suggested that increased expression of GAD65, but not GAD67, accounted for this increase. Additionally, a functional GABAergic alteration was observed in the form of increased mIPSC frequency in the KO hippocampus, indicating an increase in presynaptic GABA release. Our findings uncover a novel role for Fkbp5 in neuronal synaptic plasticity and highlight the value of Fkbp5 KO as a model for studying its role in neurological function and disease development.Item Response to Brosch et al.(Elsevier, 2012-03-07) Pihlajamäki, Jussi; Lerin, Carles; Kaminska, Dorota; Venesmaa, Sari; Itkonen, Paula; Boes, Tanner; Floss, Thomas; Schroeder, Joshua; Dearie, Farrell; Crunkhorn, Sarah; Burak, Furkan; Jimenez-Chillaron, Josep C.; Kuulasmaa, Tiina; Miettinen, Pekka; Park, Peter J.; Nasser, Imad; Zhao, Zhenwen; Zhang, Zhaiyi; Xu, Yan; Wurst, Wolfgang; Ren, Hongmei; Morris, Andrew J.; Stamm, Stefan; Goldfine, Allison B.; Laakso, Markku; Patti, Mary Elizabeth; Department of Obstetrics and Gynecology, IU School of MedicineWe would like to respond to Brosch et al. regarding our manuscript “Expression of the Splicing Factor Gene SFRS10 Is Reduced in Human Obesity and Contributes to Enhanced Lipogenesis” (Pihlajamäki et al., 2011b). Brosch performed RT-PCR in liver samples from 13 lean and 34 obese individuals, finding no differences in SFRS10 or LPIN1 expression. We wish to address points raised by Brosch, including experimental strategy and analysis of human SFRS10 expression.