B-cell activating factor involved in the pathogenesis of lupus nephritis through regulating phosphoino-sitide 3-kinase/protein kinase B/mammalian target of rapamycin signaling / 中华风湿病学杂志

ABSTRACT

Objective To investigate whether B-cell activating factor (BAFF) involved in the patho-genesis of lupus nephritis (LN) by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling. Methods Twenty-eight lupus nephritis patients and 20 controls were included in this study. The clinical data were collected. BAFF levels in plasma were measured by ELISA, and the relationship between systemic lupus erythematosus disease activity index (SLEDAI) and BAFF were analyzed. The mRNA and protein levels of BAFF, phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR) and Bcl-2 in kidney tissues were measured using real-time polymerase chain reaction (RT-PCR) and Western blotting. Data were analyzed using Mann-Whitney U test and Spearman correlation analysis. Results ①Plasma BAFF levels were significantly higher in LN patients [(580 ±45) ng/L] compared with controls [(208 ±30) ng/L](Z=-5.856, P<0.01), and significant positive correlation was found between plasma BAFF levels with SLEDAI (r=0.723, P<0.01). ② Plasma BAFF level in LN patients was positively correlated with 24 h UP and anti-dsDNA titers (r=0.381, 0.461, P<0.05). The protein level of BAFF in kidney tissues was positively correlated with 24 h UP and anti-dsDNA titer (r=0.469, 0.489, P<0.05).③The mRNA levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls[5.8±1.8 vs 2.1±0.7, Z=-4.915, P<0.01;6.7±0.9 vs 1.71±0.53, Z=-5.857, P<0.01;5.6±0.9 vs 1.8 ±0.5, Z=-5.751, P<0.01; 5.6 ±1.4 vs 1.6 ±0.4, Z=-5.291, P<0.01; 2.11 ±0.36 vs 1.33 ±0.22, Z=-4.844, P<0.01].④The protein levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls [0.72±0.19 vs 0.31±0.05, Z=-4.747, P<0.01;0.73±0.11 vs 0.33±0.09, Z=-5.834, P<0.01;0.77±0.06 vs 0.22±0.07, Z=-5.855, P<0.01;1.18±0.27 vs 0.47±0.13, Z=-5.416, P<0.01;2.08±0.37 vs 1.32±0.18, Z=-4.998, P<0.01]. Conclusion The findings of this study indicate that BAFF may participate in the pathogenesis of LN by regulating PI3K/Akt/mTOR signaling.