Protective effects of tubular liver-type fatty acid binding protein on murine IgA nephropathy
10.3760/cma.j.issn.1001-7097.2011.01.008
- VernacularTitle:肾小管肝型脂肪酸结合蛋白对小鼠IgA肾病的肾脏保护作用
- Author:
Nan ZUO
;
Yanqiu LI
;
Lining WANG
;
Zilong LI
;
Jun WANG
;
Jiangmin FENG
;
Jianfei MA
;
Qiuling FAN
;
Li YAO
- Publication Type:Journal Article
- Keywords:
Glomerulonephritis,IgA;
Fatty acid-binding proteins;
Bone marrow transplantation;
Oxidative stress
- From:
Chinese Journal of Nephrology
2011;27(1):34-40
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the renoprotection of tubular L-FABP in murine IgA nephropathy (IgAN) induced by bone marrow transplantation(BMT). Methods IgAN models were reconstituted by BMT from IgAN-prone mice into mice (Tg) transgenically tubular overexpressing human L-FABP (hL-FABP) and wild type (WT) mice. These recipients were sacrificed at 6 and 12 weeks after BMT and their kidneys were collected. The expressions of hL-FABP, fibronectin (FN)and monocyte chemoattractant protein-1 (MCP-1) mRNA were detected by real-time PCR. hL-FABP,FN, type Ⅳ collagen (Col Ⅳ ), hemeoxygenase-1 (HO-1) and 4-hydroxy-2-nonenal (4-HNE)modified proteins were detected by Western blotting. The distribution of hL-FABP and FN protein in kidney was detected by immunohistochemistry. The level of serum IgA, urinary albumin and urinary hL-FABP was detected by ELISA. Results (1) IgAN was reconstituted in both Tg and WT mice by BMT: mesangial IgA deposition and up-regulation of serum IgA. The levels were not significantly different between two groups (Tg-ddY and WT-ddY). (2) hL-FABP was expressed in proximal tubular cells of normal Tg mice. The mRNA (1.62±0.32 vs 0.46±0.09, P＜0.01) and protein expression (1.74±0.76 vs 1.14±0.31, P＜0.01) of hL-FABP was up-regulated in Tg-ddY kidney and urinary hL-FABP level (μg/g creatinine) was significantly increased (59.87±26.75 vs 31.01±14.86, P＜0.05) at the 6th week after BMT. (3) WT-ddY mice showed a significantly higher urinary albumin level (mg/L) (828±656 vs 82±22, P＜0.01), severer mesangial matrix expansion (P＜0.01),more glomerular FN and Col Ⅳ deposition at the 12th week. (4) Up-regulation of renal hL-FABP was associated with significant suppression of renal HO-1 expression (P ＜0.05),accumulation of 4-HNE modified proteins (P＜0.05) and MCP-1 mRNA expression (P＜0.01) in Tg-ddY mice. Conclusion Tubular L-FABP may lessen the progression of glomerular damage at early stages of IgAN by reducing oxidative stress and inflammatory mediators.
