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Background <p>Inflammation is a key driver in IgA nephropathy (IgAN) pathogenesis. Recent studies have demonstrated a significant association between pro-inflammatory cytokine–triggered inflammatory cascades, particularly those involving interleukin-6 (IL-6), and disease progression in IgAN. However, the underlying molecular mechanisms remain to be fully elucidated. Dioscin (DIO), a major active compound in Yiqi Qingjie Formula— a standardized formula for IgAN treatment at Guang’anmen Hospital—has shown well-defined anti-inflammatory and immunomodulatory properties.</p> Methods <p>Peripheral blood mononuclear cells (PBMCs) were isolated from 68 patients with IgA nephropathy (IgAN) and 16 healthy controls to assess key components of the IL-6 signaling pathway. An IgAN mouse model was established to evaluate the therapeutic effects of dioscin (DIO) and its potential anti-inflammatory mechanisms. The findings were further validated through complementary in vitro experiments.</p> Results <p>We observed aberrant activation of the IL-6-mediated STAT3 signaling pathway in patients with IgAN. In vitro experiments further confirmed that IL-6 promoted the secretion of galactose-deficient IgA1 (Gd-IgA1) by activating the JAK2/STAT3 axis, which downregulated the expression of the key glycosyltransferases Core 1 β1,3-galactosyltransferase (C1GalT1) and Core 1 β3GalT-specific molecular chaperone (Cosmc). Importantly, DIO significantly inhibited JAK2/STAT3 phosphorylation in IgAN model mice, a finding that was validated again in vitro.</p> Conclusion <p>This study shows that DIO reduces Gd-IgA1 production and alleviates renal injury by targeting and suppressing the IL-6-JAK2/STAT3 signaling pathway, offering a promising therapeutic strategy for IgAN.</p>

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Dioscin attenuates Gd-IgA1 overproduction by inhibiting the IL-6-JAK2/STAT3 signaling axis in IgA nephropathy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月16日

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  • Lan Lin,
  • HuiMei Li,
  • ShiQiang Zhou,
  • LiHua Zheng,
  • ShiPeng Sun,
  • Shen Li

摘要

Background

Inflammation is a key driver in IgA nephropathy (IgAN) pathogenesis. Recent studies have demonstrated a significant association between pro-inflammatory cytokine–triggered inflammatory cascades, particularly those involving interleukin-6 (IL-6), and disease progression in IgAN. However, the underlying molecular mechanisms remain to be fully elucidated. Dioscin (DIO), a major active compound in Yiqi Qingjie Formula— a standardized formula for IgAN treatment at Guang’anmen Hospital—has shown well-defined anti-inflammatory and immunomodulatory properties.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from 68 patients with IgA nephropathy (IgAN) and 16 healthy controls to assess key components of the IL-6 signaling pathway. An IgAN mouse model was established to evaluate the therapeutic effects of dioscin (DIO) and its potential anti-inflammatory mechanisms. The findings were further validated through complementary in vitro experiments.

Results

We observed aberrant activation of the IL-6-mediated STAT3 signaling pathway in patients with IgAN. In vitro experiments further confirmed that IL-6 promoted the secretion of galactose-deficient IgA1 (Gd-IgA1) by activating the JAK2/STAT3 axis, which downregulated the expression of the key glycosyltransferases Core 1 β1,3-galactosyltransferase (C1GalT1) and Core 1 β3GalT-specific molecular chaperone (Cosmc). Importantly, DIO significantly inhibited JAK2/STAT3 phosphorylation in IgAN model mice, a finding that was validated again in vitro.

Conclusion

This study shows that DIO reduces Gd-IgA1 production and alleviates renal injury by targeting and suppressing the IL-6-JAK2/STAT3 signaling pathway, offering a promising therapeutic strategy for IgAN.