9HODE Stimulates Cell Proliferation and Extracellular Matrix Synthesis in Human Mesangial Cells via PPARγ
| Autor: | Masatomo Mori, Hiroyuki Shimizu, Shuichi Okada, Fumikazu Okajima, Atsushi Kuwabara, Mayumi Negishi |
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| Rok vydání: | 2004 |
| Předmět: |
Collagen Type IV
0301 basic medicine Blotting Western Biology General Biochemistry Genetics and Molecular Biology Extracellular matrix 03 medical and health sciences Type IV collagen chemistry.chemical_compound 0302 clinical medicine Humans Linoleic Acids Conjugated Receptor Cells Cultured Flavonoids Cell growth Oligonucleotides Antisense Molecular biology Deoxyuridine Extracellular Matrix Fibronectins Glomerular Mesangium Fibronectin Blot 030104 developmental biology chemistry 030220 oncology & carcinogenesis Calcium-Calmodulin-Dependent Protein Kinases biology.protein Oxidation-Reduction Cell Division Lipoprotein |
| Zdroj: | Experimental Biology and Medicine. 229:1053-1060 |
| ISSN: | 1535-3699 1535-3702 |
| DOI: | 10.1177/153537020422901010 |
| Popis: | Plasma oxidized low-density lipoprotein (OX-LDL) levels are elevated in patients with renal diseases, including diabetic nephropathy. We examined effects of OX-LDL on cell proliferation and extracellular matrix (ECM) production by using normal human mesangial cells. Furthermore, we examined possible involvement of peroxisome proliferator-activated receptor gamma (PPARgamma). Mesangial cell proliferation with OX-LDL, 9-hydroxy-10,12-octadecadienoic acid (9HODE), and 13-hydroxy-9,11-octadecadienoic acid (13HODE), the major components of OX-LDL, were determined by 5-bromo-2'-deoxyuridine (BrdU) or 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) incorporation. The effect of OX-LDL on mesangial cell proliferation with PD98059 pretreatment was determined by BrdU incorporation. Type IV collagen, fibronectin, and PPARgamma expression with OX-LDL or 9HODE or 13HODE was determined by Western blotting. Type IV collagen expression with antisense oligonucleotide against PPARgamma pretreatment was also determined by Western blotting. The effect of PD98059 pretreatment on PPARgamma expression was determined by Western blotting. In mesangial cells exposed to isolated OX-LDL from human plasma, BrdU incorporation was increased, and this increase was deleted by PD98059. Type IV collagen expression was significantly increased by OX-LDL. 9HODE and 13HODE increased BrdU and MTT incorporation into mesangial cells and also increased expressions of Type IV collagen and fibronection, the major components of ECM. PPARgamma expression in mesangial cells was stimulated by 9HODE. The reduction of PPARgamma synthesis by pretreatment of antisense oligonucleotide against PPARgamma remarkably attenuated Type IV collagen synthesis induced by 9HODE. PPARgamma expression induced by 9HODE was also reduced by PD98059 pretreatment. These findings demonstrate that 9HODE, the major component of OX-LDL, stimulates cell proliferation and ECM production of human mesangial cells. In addition, the stimulatory effects are, at least in part, mediated by PPARgamma, which may exist in downstream of ERK1/2 pathway. |
| Databáze: | OpenAIRE |
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