Hydrogen peroxide-inducible clone-5 regulates mesangial cell proliferation in proliferative glomerulonephritis in mice
Autor: | Joo-ri Kim-Kaneyama, Akira Miyazaki, Shoji Kagami, Ariunbold Jamba, Shuji Kondo, Takashi Nagai, Maki Urushihara |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male endocrine system Primary Cell Culture Cell Becaplermin lcsh:Medicine Apoptosis Biology Nephrectomy Transforming Growth Factor beta1 Mice Glomerulonephritis Crotalid Venoms medicine Animals Humans Trimeresurus Cyclin D1 Receptor lcsh:Science Cell Proliferation Mice Knockout Multidisciplinary Cell growth lcsh:R Proto-Oncogene Proteins c-sis LIM Domain Proteins medicine.disease Molecular biology Glomerular Mesangium DNA-Binding Proteins Cytoskeletal Proteins Ki-67 Antigen medicine.anatomical_structure Gene Expression Regulation Cell culture Mesangial Cells Female lcsh:Q Signal transduction Research Article Signal Transduction Transforming growth factor |
Zdroj: | PLoS ONE, Vol 10, Iss 4, p e0122773 (2015) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor (TGF)-β1-inducible focal adhesion protein. We previously demonstrated that Hic-5 was localized in mesangial cells and its expression was associated with glomerular cell proliferation and matrix expansion in human and rat glomerulonephritis (GN). In the present study, we first assessed the role of Hic-5 in mesangioproliferative GN by injecting Habu venom into heminephrectomized wild type (Hic-5+/+) and Hic-5-deficient (Hic-5-/-) mice. Hic-5+/+ GN mice exhibited glomerular cell proliferation on day 7. Surprisingly, glomerular cell number and Ki-67-positive cells in Hic-5-/- GN mice were significantly greater than those in Hic-5+/+ GN mice on day 7, although the number of glomerular apoptotic cells and the expression of growth factors (platelet-derived growth factor-BB and TGF-β1) and their receptors were similarly increased in both Hic-5+/+ and Hic-5-/- GN mice. In culture experiments, proliferation assays showed that platelet-derived growth factor-BB and TGF-β1 enhanced the proliferation of Hic-5-/- mesangial cells compared with Hic-5+/+ mesangial cells. In addition, mitogenic regulation by Hic-5 was associated with altered and coordinated expression of cell cycle-related proteins including cyclin D1 and p21. The present results suggest that Hic-5 might regulate mesangial cell proliferation in proliferative GN in mice. In conclusion, modulation of Hic-5 expression might have a potential to prevent mesangial cell proliferation in the acute mitogenic phase of glomerulonephritis. |
Databáze: | OpenAIRE |
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