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HMGB1 Mediate Extracellular Matrix Deposition of Glomerular Mesangial Cell of Lupus Nephritis through Combining with RAGE
Yang Ran1#, Tian Yuexin1#, Zhao Lu1, Miao Xinyan1, Feng Xiaojuan1, Li Yuzhe1, Zhu Yuanjun2, Wang Ziwei1, Liu Shuxia1*
1Department of Pathology, Hebei Medical University, Shijiazhuang 050017, China; 2Physical Examination Center, Hebei General Hosptial, Shijiazhuang 050017, China
Abstract: Lupus nephritis (LN) is the most frequent visceral complication of SLE， accounting for an increased morbidity， including end stage renal disease and mortality. Above all， it is an important significance to explore the mechanism of LN and look for personalized treatment options. Our previous researches had revealed that HMGB1 was significantly increased in renal tissue and correlated with the renal glomeruli proliferation in MRL/Faslpr mice. In this study， we want to further explore the realtionship between HMGB1 and extracellular matrix deposition of renal glomeruli with lupus nephritis. Plasmas from patients with LN and glycyrrhizinic acid， a specific inhibitor of HMGB1， were used to infer the role of HMGB1 in extracellular matrix deposition of HMC; renopuncture tissues were used to revealed the correlationship of RAGE and Collagen IV; human recombinant His- HMGB1 and Box A， a specific inhibitor of RAGE， were used to infer the mechanism of HMGB1 in extracellular matrix deposition of HMC. The ELISA result showed that compared with control group， the expression of FN protein in LN palsma group was increased and the secretion of FN in Gly+LN palsma group was downregulated compared with LN palsma group， indicated that the Gly blocked the FN secretion induced by plasma from patients with LN; the secretion of FN in HMC of Box A+His-HMGB1 group was decreased compared with His-HMGB1 group， which showed that Box A blocked the FN secretion induced by His-HMGB1. The immunohistochemical result showed that the expression of RAGE protein in renopuncture tissues of patients with LN was upregulated and showed statistic correlation with the expression of Collagen IV. The Western blot result showed that the expression of RAGE protein in HMC was upregulated by His-HMGB1 compared with control group. The IP result revealed that the combine of RAGE and His-HMGB1 protein in HMC. In conclusion， HMGB1 mediate the extracellular matrix deposition of glomerular mesangial cell of LN through combining with RAGE.
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