Protective effects of tubular liver-type fatty acid binding protein on murine IgA nephropathy / 中华肾脏病杂志
Chinese Journal of Nephrology
;
(12): 34-40, 2011.
Article
in Chinese
| WPRIM
| ID: wpr-382851
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Chinese Journal of Nephrology
Year:
2011
Type:
Article
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