6 results on '"Rabson, Arnold B."'
Search Results
2. An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells.
- Author
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Chen, Qing, Shou, Peishun, Zhang, Liying, Xu, Chunliang, Zheng, Chunxing, Han, Yanyan, Li, Wenzhao, Huang, Yin, Zhang, Xiaoren, Shao, Changshun, Roberts, Arthur I., Rabson, Arnold B., Ren, Guangwen, Zhang, Yanyun, Wang, Ying, Denhardt, David T., and Shi, Yufang
- Subjects
OSTEOPONTIN ,ADIPOGENESIS ,BONE growth ,ARGININE ,ASPARTATES - Abstract
An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, and integrin αv/β1 plays a critical role in the lineage determination of MSCs. Although OPN is a well-established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re-expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN
−/− MSCs. Retarded bone formation by OPN−/− MSCs was also verified by in vivo implantation with hydroxyapatite-tricalcium phosphate, a bone-forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well-known OPN receptors integrin αv/β1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin αv/β1. Consistent with these in vitro results, OPN−/− mice had a higher fat to total body weight ratio than did wild-type mice. Therefore, our study demonstrates a novel role for OPN-integrin αv/β1 in regulating MSC differentiation. S tem C ells 2014;32:327-337 [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
3. Caloric restriction reduces growth of mammary tumors and metastases.
- Author
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De Lorenzo, Mariana S., Baljinnyam, Erdene, Vatner, Dorothy E., Abarzúa, Patricio, Vatner, Stephen F., and Rabson, Arnold B.
- Subjects
TUMOR growth prevention ,LOW-calorie diet ,METASTASIS ,CANCER cell proliferation ,BREAST cancer ,SOMATOMEDIN ,ADIPONECTIN ,LABORATORY mice ,PREVENTION - Abstract
We investigated the effects of caloric restriction (CR) on growth of tumors and metastases in the 4T1 mammary tumor model and found that CR, compared with normal diet, reduced the growth of mammary tumors and metastases and the total number of metastases that originated both spontaneously from the primary tumor and also experimentally from i.v. injection of the tumor cells. CR also decreased proliferation and angiogenesis and increased apoptosis in tumors. CR reduced levels of insulin, leptin, insulin-like growth factor 1, insulin-like growth factor binding protein 3 and increased adiponectin in tumors. We also demonstrated that tumors from CR mice possessed lower levels of transforming growth factor-β, lower intratumor deposition of collagen IV and reduced invasiveness due to a decrease in tumor secretion of active matrix metalloproteinase 9. Our results suggest that CR-induced metabolic and signaling changes affect the stroma and the tumor cells resulting in a microenvironment that prevents proliferation of breast tumors and their metastases. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
4. MEOX2 regulates nuclear factor-κB activity in vascular endothelial cells through interactions with p65 and IκBβ.
- Author
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Chen, Yun, Rabson, Arnold B., and Gorski, David H.
- Subjects
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BLOOD-vessel development , *TUMORS , *NF-kappa B , *VASCULAR endothelial growth factors , *NEOVASCULARIZATION - Abstract
Aims Tumours secrete proangiogenic factors to induce the ingrowth of blood vessels, the end targets of which are vascular endothelial cells (ECs). The MEOX2 homeoprotein inhibits nuclear factor-κB (NF-κB) signalling and EC activation in response to serum and proangiogenic factors. We hypothesize that MEOX2 interacts with components of this pathway in vascular ECs to modulate NF-κB activity and EC activation and that these interactions depend upon specific domains within the MEOX2 protein. Methods and results To test our hypothesis, we transduced ECs with MEOX2 expression constructs. MEOX2 protein localized to the nuclear fraction, as did IκBβ and p65. By co-immunoprecipitation, MEOX2 bound to both p65 and IκBβ. Immuno-fluorescence demonstrated that MEOX2 colocalizes in the nucleus with both p65 and IκBβ and that this colocalization requires the MEOX2 homeodomain and N-terminal domain. Finally, promoter assays revealed that MEOX2 expression has a biphasic effect on NF-κB-dependent promoters. At low levels, MEOX2 stimulates NF-κB activity, whereas at high levels, it represses, effects that also depend upon the homeodomain and the N-terminal domain. Conclusion Our results represent the first report of an interaction between a homeobox protein and IκBβ and suggest that MEOX2 modulates the activity of the RelA complex through direct interaction with its components. These observations implicate MEOX2 as a potentially important regulatory gene inhibiting not only the angiogenic response of ECs to proangiogenic factors, but also their response to chronic inflammatory stimulation that normally activates NF-κB, suggesting MEOX2 as a possible molecular target for the therapy of angiogenesis-dependent diseases such as cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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- View/download PDF
5. Species Variation in the Mechanisms of Mesenchymal Stem Cell- Mediated Immunosuppression.
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Guangwen Ren, Juanjuan Su, Liying Zhang, Xin Zhao, Weifang Ling, L'Huillie, Andrew, Jimin Zhang, Yongqing Lu, Roberts, Arthur I., Weizhi Ji, Huatang Zhang, Rabson, Arnold B., and Yufang Shi
- Subjects
STEM cells ,IMMUNOSUPPRESSION ,NITRIC oxide ,CHEMOKINES ,IMMUNOLOGIC diseases ,THERAPEUTICS - Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) hold great promise for treating immune disorders because of their immunoregulatory capacity, but the mechanism remains controversial. As we show here, the mechanism of MSC-mediated immunosuppression varies among different species. Immunosuppression by human- or monkey-derived MSCs is mediated by indoleamine 2,3-dioxygenase (IDO), whereas mouse MSCs utilize nitric oxide, under the same culture conditions. When the expression of IDO and inducible nitric oxide synthase (iNOS) were examined in human and mouse MSCs after stimulation with their respective inflammatory cytokines, we found that human MSCs expressed extremely high levels of IDO, and very low levels of iNOS, whereas mouse MSCs expressed abundant iNOS and very little IDO. Immunosuppression by human MSCs was not intrinsic, but was induced by inflammatory cytokines and was chemokine-dependent, as it is in mouse. These findings provide critical information about the immunosuppression of MSCs and for better application of MSCs in treating immune disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
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6. HIV-1 Infection of First-Trimester and Term Human Placental Tissue: A Possible Mode of Maternal-Fetal Transmission.
- Author
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Maury, Wendy, Potts, Barbara J., and Rabson, Arnold B.
- Abstract
To understand the potential role of placental tissue in the pathogenesis of neonatal AIDS, the distribution of human immunodeficiency virus type 1 (HIV-l) receptor and the infectability of placental tissue by HIV-l were studied. Both the mRNA and the protein for the HIV receptor (CD4) were present in fetal-derived placenta. By immunofluorescent microscopy, a number of different cell types appeared to be CD4+; positive cells were observed in the lining and stroma of the chorionic villi. Some of these CD4+ cells dual-labeled with the trophoblastic marker placental lactogen. In addition, CD4+ cells were observed within the lining of placental blood vessels. Organ cultures of first-trimester and term placentas were infectable by HIV as monitored by reverse transcriptase activity of culture supernatants and by immunofluorescent labeling of HIV antigens. One potential route of congenital HIV transmission may be direct placental infection by HIV as early as the first trimester, with subsequent transplacental spread of the virus. [ABSTRACT FROM PUBLISHER]
- Published
- 1989
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