| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Lee, Saseong De Falco, Sandro Cho, Chul-Soo Yoo, Seung-Ah Oh, Sang-Min Park, Ji-Hwan Rho, Sangchul Hwang, Daehee Cicatiello, Valeria Hwang, Seong-Hye Kim, Wan-Uk |
| Description |
Author Affiliation: Yoo SA ( Pohang University of Science and Technology-Catholic Biomedical Engineering Institute, Catholic University of Korea, Seoul 137-701 Korea); Park JH ( Department of Chemical Engineering, Pohang University of Science and Technology, Pohang 790-784, Korea); Hwang SH ( Pohang University of Science and Technology-Catholic Biomedical Engineering Institute, Catholic University of Korea, Seoul 137-701 Korea); Oh SM ( Pohang University of Science and Technology-Catholic Biomedical Engineering Institute, Catholic University of Korea, Seoul 137-701 Korea); Lee S ( Pohang University of Science and Technology-Catholic Biomedical Engineering Institute, Catholic University of Korea, Seoul 137-701 Korea); Cicatiello V ( Istituto di Genetica e Biofisica Adriano Buzzati-Traverso, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy); Rho S ( Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873 Korea); De Falco S ( Istituto di Genetica e Biofisica Adriano Buzzati-Traverso, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy); Hwang D ( Bio-Ker, MultiMedica Group, 80131 Naples, Italy); Cho CS ( Pohang University of Science and Technology-Catholic Biomedical Engineering Institute, Catholic University of Korea, Seoul 137-701 Korea); Kim WU ( Pohang University of Science and Technology-Catholic Biomedical Engineering Institute, Catholic University of Korea, Seoul 137-701 Korea) |
| Abstract |
Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have promigratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. In this study, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with small interfering RNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and neuropilin-1, and upregulating the expression of antiapoptotic molecules, pErk and Bcl2. Knockdown of PlGF transcripts reduced RA-FLS proliferation in a xenotransplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
6 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-03-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cell Movement Genetics Cell Proliferation Pregnancy Proteins Synovial Membrane Metabolism Apoptosis Drug Effects Arthritis, Rheumatoid Pathology Blotting, Western Cell Survival Cells, Cultured Fibroblasts Gene Expression Profiling Hek293 Cells Hyperplasia Microscopy, Confocal Neovascularization, Pathologic Oligonucleotide Array Sequence Analysis Pharmacology Primary Cell Culture Rna Interference Reverse Transcriptase Polymerase Chain Reaction Blood Supply Vascular Endothelial Growth Factor Receptor-1 Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
