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  • Title: Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy.
    Author: Liang Y, Zhang J, Zhou Y, Xing G, Zhao G, Liu Z.
    Journal: Cell Physiol Biochem; 2015; 36(5):1793-1808. PubMed ID: 26184511.
    Abstract:
    BACKGROUND/AIMS: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, and often aggravates by mucosal infection. Secretory IgA (SIgA) is the dominant immunoglobulin in mucosal immunity, and is deposited in the mesangium in IgAN. The biological effects of SIgA on mesangial cells are poorly understood. METHODS: Deposition of SIgA in frozen renal sections from IgAN patients was detected and the association between deposition of SIgA and patients characteristics was analyzed. The biological effects of SIgA and polymeric IgA (pIgA) on human renal mesangial cells were compared. We also studied the molecular mechanism of microRNA regulating the inflammatory effects of SIgA on mesangial cells. RESULTS: Fifty-five of 176 patients had SIgA deposition with higher incidence of infection history and hematuria, lower serum cystatin C, β2 microglobulin, blood urea nitrogen and T-grade in the Oxford classification, compared with patients without SIgA deposition. SIgA stimulated mesangial cells at a higher ratio of proliferation and higher production of interleukin (IL)-6, IL-8, monocyte chemotactic protein 1, transforming growth factor-β1 and fibronectin, compared with SIgA from healthy volunteers. The proliferation and cytokines production in mesangial cells stimulated by SIgA were significantly lower than that stimulated by pIgA. miR- 16 targeted the 3′-untranslated region of IL-6 and suppressed its translation in mesangial cells induced by SIgA. CONCLUSIONS: The biological effects of SIgA on mesangial cells differ from those of pIgA. SIgA stimulates mesangial cell proliferation and production of proinflammatory cytokines. IL-6 production is regulated by miR-16 in mesangial cells.
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