title: Curcumin prevents diabetic nephropathy against inflammatory response via reversing caveolin-1 Tyr14 phosphorylation influenced TLR4 activation.
abstract: Inflammation is involved in the development and/or progression of diabetic nephropathy (DN). Curcumin has been reported for its anti-inflammation activity in DN. However, the mechanisms involved in the renoprotective effects of curcumin have not been clearly demonstrated. In this study, we hypothesized that curcumin affected high glucose (HG)-induced inflammation profiles in vivo and in vitro and then prevented renal injury in diabetic rats via reversing cav-1 Tyr(14) phosphorylation that influenced TLR4 activation. Streptozotocin (STZ)-induced diabetic rats received vehicle or curcumin for twelve weeks and podocytes were treated with HG in the presence or absence of curcumin in vitro. To further evaluate the effect of cav-1 phosphorylation at Tyr(14) on HG-induced podocyte inflammation response and TLR4 activation, a recombinant plasmid GFP-Cav-1 Y14F with a mutated phosphorylation site of cav-1, was transfected into cultured podocytes. In vivo, curcumin improved histological abnormalities and fibrosis of a diabetic kidney, inhibited renal inflammatory gene expression and reduced cav-1 phosphorylation at Tyr(14) and the expression of TLR4. Pretreatment of podocytes with curcumin reduced HG-stimulated production of proinflammatory cytokines, TLR4 and the phosphorylation of cav-1. But immunohistochemistry in rat kidney showed that the elevation of TLR4 expression is more evident in the renal interstitum than in the glomerulus where podocytes are located, and the possibility that the anti-inflammatory effects of curcumin on other cells in the kidney may be mediated through the same molecular pathways as in podocytes. Our study suggests that curcumin treatment ameliorates DN via inhibition of inflammatory gene expression by reversing caveolin-1 Tyr(14) phosphorylation that influenced TLR4 activation.
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Sun
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Lv
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China.
authors.forename: Xiang-Chun
authors.initials: XC
authors.lastname: Liu
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: guangj@sdu.edu.cn.
authors.forename: Guang-Ju
authors.initials: GJ
authors.lastname: Guan
authors.affiliation: Nephrology Research Institute of Shandong University, The Second Hospital of Shandong University, Shandong University, Jinan, Shandong, China. Electronic address: gangliu@sdu.edu.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003474:Curcumin / Q000008:administration & dosage*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000276:immunology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000276:immunology; D003927:Diet, Diabetic / Q000009:adverse effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D050199:Podocytes / Q000187:drug effects / Q000502:physiology; D015202:Protein Engineering; D051381:Rats; D017208:Rats, Wistar; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D051242:Caveolin 1; D051197:Toll-Like Receptor 4; D014443:Tyrosine; D003474:Curcumin
keywords: Caveolin-1; Curcumin; Cytokines; Macrophage; TLR4