Department of Nephrology, Peking University Third Hospital, Beijing 100191, P.R. China.
Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing 100191, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5272-5282. doi: 10.3892/mmr.2018.8544. Epub 2018 Feb 2.
IgA nephropathy (IgAN) is characterized by predominant IgA deposition in the glomerular mesangium. It has been considered that the deposited IgA is synthesized by B cells, although recent reports have suggested the implication of other cell types. Therefore, the present study investigated whether glomerular mesangial cells could produce IgA by themselves. Semi‑quantitative reverse transcription-polymerase chain reaction, and immunostaining analysis revealed that the IgA protein and gene transcripts were expressed in primary human renal mesangial cells (HRMCs). Furthermore, the IgA heavy chain (α1 and α2) and the light chain (κ and λ) were localized in the cytoplasm or were located on the cell membranes of human mesangial cells (HMCs). Mass spectrometry results indicated that Ig α1 and Ig α2 were secreted in the culture media of HMCs. The transcripts of Ig α, Ig κ and Ig λ constant regions were detected. The predominant rearrangement pattern of the variable region of Ig κ, was Vκ3‑2001/Jκ101 in HMCs and Vκ1‑1201/Jκ401 in HRMCs. In addition, knockdown of Ig α1 expression by small interfering RNA (siRNA) inhibited cell adhesion and promoted apoptosis. Our findings demonstrate that HMCs can express IgA, and that this expression is associated with cell functions, which may contribute to the deposition of IgA in patients with IgAN.
IgA 肾病(IgAN)的特征是肾小球系膜中主要沉积 IgA。尽管最近的报告表明其他细胞类型也有牵连,但人们一直认为沉积的 IgA 是由 B 细胞合成的。因此,本研究探讨了肾小球系膜细胞是否可以自行产生 IgA。半定量逆转录聚合酶链反应和免疫染色分析显示,人原代肾小球系膜细胞(HRMC)中表达 IgA 蛋白和基因转录本。此外,IgA 重链(α1 和 α2)和轻链(κ 和 λ)定位于细胞质中,或位于人系膜细胞(HMC)的细胞膜上。质谱结果表明 Igα1 和 Igα2 分泌到 HMC 的培养物中。检测到 Igα、Igκ 和 Igλ 恒定区的转录本。Igκ 可变区的主要重排模式为 HMC 中的 Vκ3-2001/Jκ101 和 HRMC 中的 Vκ1-1201/Jκ401。此外,小干扰 RNA(siRNA)下调 Igα1 表达可抑制细胞黏附和促进细胞凋亡。我们的研究结果表明,HMC 可以表达 IgA,并且这种表达与细胞功能有关,这可能导致 IgAN 患者中 IgA 的沉积。