HMGB1/TLR4 mediates proliferation and extracellular matrix deposition of glomerular mesangial cells in LN / 中国药理学通报

ABSTRACT

Aim To investigate the mechanism of the mediation of high mobility group protein BI (HMGB1) and Toll like receptor 4 (TLR4) in the proliferation and extracellular matrix deposition of glomerular mesangial cells in lupus nephritis. Methods Immunohistochemistry and immunocytochemistry were employed to detect the TLR4 expression levels in the LN clinical specimens and MRL/lpr mice. Western blot was used to detect the TLR4 and Myd88 expression levels in human mesangial cells stimulated by recombinant HMGB1. Cell counting kit-8, Western blot and ELISA were employed to detect the proliferation and FN expression levels in HMCs stimulated by the exchange plasma of LN patients. Results Immunohistochemistry and immunocytochemistry results showed that compared with control groups,the expression levels of TLR4 in glomeruli cells of LN patients and MRL/lpr mice were up-regulated. Western blot showed that compared with control groups, the expression levels of TLR4 and Myd88 increased in HMCs stimulated by recombinant HMGB1. While the inhibition of HMGB1 and TLR4 both improved the proliferation, FN synthesis and FN secretion of HMCs induced by the exchange plasma of LN patients (both P < 0. 05). Conclusion HMGB1 may participate in the pathogenesis of LN by activating TLR4 to mediate the proliferation and extracellular matrix deposition of mesangial cells.