Glucocorticoid diminishes vascular endothelial growth factor and exacerbates proteinuria in rats with mesangial proliferative glomerulonephritis.
Glucocorticoids are widely prescribed for renal diseases. It is believed that glucocorticoids attenuate immune-mediated renal diseases by suppressing the cell-mediated immune system. However, there is evidence that glucocorticoids influence the expression of such growth factors as vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and connective tissue growth factor (CTGF), which are known to influence the development or progression of renal diseases. Therefore, we undertook this study to determine whether glucocorticoids regulate proteinuria or extracellular matrix (ECM) production by altering these growth factors. Mesangial proliferative glomerulonephritis was induced in rats by intravenous injection of monoclonal antibody (OX-7), and dexamethasone (20 mg/kg) was administered intraperitoneally from the third to seventh disease day. Glomerular expression of VEGF, TGF-beta1, and CTGF, the amount of urinary protein, and glomerular ECM were measured on the seventh disease day. The nephritic group showed proteinuria and greater VEGF, TGF-beta1, and ECM production. Dexamethasone aggravated proteinuria (protein, 0.4 +/- 0.1 mg/mg creatinine in the NC group, 6.3 +/- 2.0 mg/mg creatinine in the DC group, and 21.1 +/- 1.9 mg/mg creatinine in the D-Dex group; P < 0.05) and diminished VEGF release (22 +/- 3 pg/mg total protein in the NC group, 292 +/- 26 pg/mg total protein in the DC group, and 198 +/- 23 pg/mg total protein in the D-Dex group; P < 0.05). Expression of TGF-beta1, CTGF, and ECM was not altered significantly by dexamethasone treatment. We found that glucocorticoid diminishes VEGF release and at the same time exacerbates proteinuria in rats with this type of glomerulonephritis.
Ha
Il Soo
IS
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea. ilsooha@snu.ac.kr
Um
Eun Young
EY
Jung
Hae Ryoung
HR
Park
Hye Won
HW
Cheong
Hae Il
HI
Choi
Yong
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D055513:Connective Tissue Growth Factor; D003404:Creatinine / Q000097:blood; D004326:Drinking / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006133:Growth Substances / Q000096:biosynthesis; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018800:Thy-1 Antigens / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D014554:Urination / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; C526316:CCN2 protein, rat; D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D006133:Growth Substances; D017874:Immediate-Early Proteins; D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D018800:Thy-1 Antigens; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D055513:Connective Tissue Growth Factor; D003404:Creatinine