title: Role of PI3K/Akt signal pathway on proliferation of mesangial cell induced by HMGB1.
abstract: Mesangial cell (MC) proliferation is an important event in LN. Our previous studies have shown that extracellular High Mobility Group Box-1 protein (HMGB1) plays a critical role in pathophysiological mechanism of lupus nephritis (LN) and HMGB1 could induce MC proliferation. The purpose of this study is to investigate the effect of phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway activation on mesangial cell proliferation induced by HMGB1 and whether Toll-like receptor 2 (TLR2) plays an important role in this progress. The results showed that HMGB1 induced overexpression of p85, p110 and p-Akt in mouse mesangial cell (MMC) and increased the proliferative level of MMC cells. In addition, HMGB1 induced a physical interaction between TLR2 and p85. The TLR2 neutralization antibody and LY294002 both reduced the MMC proliferation levels induced by HMGB1 and also blocked the HMGB1-dependent phosphorylation of the Akt. Thus, HMGB1 increases interaction between TLR2 with p85 and in sequence phosphorylates Akt at ser473, thereafter mediates MMC proliferation, which contributed significantly to the pathophysiology of MMCs dysfunction.
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pathology, Shijiazhuang people's medical college, Shijiazhuang.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University.
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University.
authors.forename: Jinxi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University; Department of Pathology, Shijiazhuang people's medical college, Shijiazhuang.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The 2nd hospital of Hebei medical University, Shijiazhuang.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Pathology, Hebei general hospital, Shijiazhuang.
authors.forename: Lin
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Nephrology, Shengnongju Hospital of Huanghua city, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University. Electronic address: susanliu2001@hotmail.com.
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D058534:Class I Phosphatidylinositol 3-Kinases; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D016326:Extracellular Matrix Proteins; D024243:HMGB1 Protein; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D051195:Toll-Like Receptor 2; C094556:Ecm1 protein, mouse; C421683:Pik3cd protein, mouse
keywords: HMGB1; Lupus nephritis; MMC proliferation; PI3K/Akt; TLR2