Mesangial cell-derived tumor necrosis factor α up-regulates the expression of tubular liver type fatty acid binding-protein and its renoprotective role in IgA nephropathy
10.3760/cma.j.issn.1001-7097.2011.07.001
- VernacularTitle:系膜细胞源性肿瘤坏死因子α上调IgA肾病肾小管肝型脂肪酸结合蛋白的表达及其肾脏保护作用
- Author:
Nan ZUO
;
Xiaoli 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,liver-type;
Oxidative stress;
Glomerulotubular cross-talk
- From:
Chinese Journal of Nephrology
2011;27(7):469-474
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of up-regulation of tubular liver-type fatty acid binding-protein (L-FABP) in IgA nephropathy (IgAN) and its renoprotective role.Methods Murine mesangial cells (MCs) from primary cell culture were cultured with aggregated IgA (AIgA) (10 to 250 mg/L) for 48 hours. The supernatant after culture was collected as AIgA-MC medium. Murine proximal tubular cell line (mProx) stably expressing human L-FABP (hL-FABP) by transfection (mProx-L) were cultured with AIgA, AIgA-MC medium and /or neutralizing anti-TNF-α antibody and recombinant murine TNF-α, respectively. AIgA-MC medium (AIgA final concentration was 25 mg/L) was cultured with mProx and mProx-L cells. The mRNA expressions of hL-FABP and MCP-1 of the cells were detected by real-time PCR. The protein expressions of hL-FABP and 4-HNE of the cells were detected by Western blotting. Results (1) The hL-FABP mRNA and protein expression stimulated by AIgA-MC medium was significantly higher as compared to AIgA (P＜0.01). (2) Pre-incubation of neutralizing anti-TNF-α antibody (final concentration was 1 and 5 mg/L) with mProx-L cells could significantly suppress the up-regulation of hL-FABP protein expression induced by AlgA-MC medium (P＜0.05 and P＜0.01).(3) Recombinant murine TNF-α (final concentration was 50 and 250 ng/L) also induced a significant up-regulation of hL-FABP expression (P＜0.01). (4) After the stimulation of AIgA-MC medium, both 4-HNE protein expression and MCP-1 mRNA expression were significantly suppressed in mProx-L cells compared to those of mProx cells (P ＜0.05 and P＜0.01). Conclusion Mesangial cell-derived TNF-α can induce up-regulation of tubular L-FABP expression. Overexpression of tubular L-FABP may lessen the progression of IgAN by reducing oxidative stress and inflammatory mediators.
