The aim of the present study was to investigate the involvement of B cell‑activating factor (BAFF) in the pathogenesis of IgA nephropathy by activating the tumor necrosis factor receptor‑associated factor 6 (TRAF6)/NF‑κB signaling pathway in glomerular mesangial cells. For the clinical analysis, blood, urine and kidney tissue samples were collected from 58 patients diagnosed with primary IgA nephropathy by renal biopsy. For the in vitro study, glomerular mesangial cells were divided into five groups: Control (con)‑short hairpin RNA (shRNA) (control group); con‑shRNA + BAFF (20 ng/ml); con‑shRNA + BAFF + BAFF‑RFc chimera protein (500 µg/ml); TRAF6‑shRNA; and TRAF6‑shRNA + BAFF (20 ng/ml). For the in vivo experiments, 60 Sprague‑Dawley rats were randomly divided into four groups: Con‑small interfering RNA (siRNA) (control group); con‑siRNA + IgA (IgA nephropathy group), BAFF‑RFc chimera protein (2 µg/ml) + IgA, and TRAF6‑siRNA (0.2 µM) + IgA. Reverse transcription‑quantitative PCR was performed to evaluate the mRNA expression levels of TRAF6, connective tissue growth factor (CTGF), fibronectin (FN) and NF‑κBP65. Western blot analysis was used to detect the protein expression levels of TRAF6, FN, CTGF and phosphorylated‑NF‑κBP65 in glomerular mesangial cells and kidney tissues. The results revealed that plasma BAFF levels were positively correlated with the severity of pathological damage in patients with IgA nephropathy. In vitro, BAFF induced the mRNA and protein expression of TRAF6, CTGF, FN and NF‑κBP65 in glomerular mesangial cells. After the BAFF‑RFc chimera protein was added to inhibit the binding of BAFF and BAFF‑receptor (‑R), this effect was reduced. In vivo, inhibition of the effects of BAFF via injection with the BAFF‑R Fc chimera protein reduced kidney damage in rats suffering from IgA nephropathy. The effect on the expression of signaling pathway‑associated proteins was also alleviated. In conclusion, BAFF enhanced the expression of fibroblast factors in the kidneys by activating the TRAF6/NF‑κB signaling pathway.
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【BAFF is involved in the pathogenesis of IgA nephropathy by activating the TRAF6/NF‑κB signaling pathway in glomerular mesangial cells.].
【BAFF通过激活肾小球系膜细胞中的TRAF6 /NF-κB信号通路参与IgA肾病的发病机制。】
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DOI：10.3892/mmr.2019.10870文章类型：杂志文章
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：本研究的目的是通过激活肾小球系膜中的肿瘤坏死因子受体相关因子6（TRAF6）/NF-κB信号通路，研究B细胞激活因子（BAFF）在IgA肾病发病机制中的参与细胞。为了进行临床分析，收集了58例经肾活检诊断为原发性IgA肾病的患者的血液，尿液和肾脏组织样本。对于体外研究，将肾小球系膜细胞分为五组：对照组（con）-短发夹RNA（shRNA）（对照组）；肾小球系膜细胞（shRNA）。 con‑shRNA BAFF（20 ng / ml）； con‑shRNA BAFF BAFF‑RFc嵌合蛋白（500 µg / ml）； TRAF6-shRNA；和TRAF6‑shRNA BAFF（20 ng / ml）。对于体内实验，将60只Sprague-Dawley大鼠随机分为四组：超小型干扰RNA（siRNA）（对照组）； con‑siRNA IgA（IgA肾病组），BAFF‑RFc嵌合蛋白（2 µg / ml）IgA和TRAF6‑siRNA（0.2 µM）IgA。进行逆转录定量PCR评估TRAF6，结缔组织生长因子（CTGF），纤连蛋白（FN）和NF-κBP65的mRNA表达水平。 Western blot分析用于检测肾小球系膜细胞和肾组织中TRAF6，FN，CTGF和磷酸化的NF-κBP65的蛋白表达水平。结果显示，血浆BAFF水平与IgA肾病患者的病理损害严重程度呈正相关。在体外，BAFF诱导肾小球系膜细胞中TRAF6，CTGF，FN和NF-κBP65的mRNA和蛋白表达。加入BAFF‑RFc嵌合蛋白以抑制BAFF和BAFF受体（‑R）结合后，这种作用减弱了。在体内，通过注射BAFF‑R Fc嵌合蛋白抑制BAFF的作用可减少IgA肾病大鼠的肾脏损害。也减轻了对信号通路相关蛋白表达的影响。总之，BAFF通过激活TRAF6 / NF‑κB信号通路增强了肾脏中成纤维细胞因子的表达。
