title: Purple corn anthocyanins dampened high-glucose-induced mesangial fibrosis and inflammation: possible renoprotective role in diabetic nephropathy.
abstract: Purple corn has been classified as a functional food rich in anthocyanins possessing potential disease-preventive properties. This study examined whether purple corn anthocyanins (PCA) mainly comprised cyanidin 3-glucoside and cyanidin-3-(6″-malonylglucoside) can attenuate high-glucose (HG)-promoted mesangial cell (MC) proliferation and matrix accumulation, major features of diabetic glomerulosclerosis. Human renal MC were cultured for 3 days in media containing 5.5 mM glucose plus 27.5 mM mannitol as osmotic controls or media containing 33 mM glucose in the absence and presence of 1-20 μg/ml PCA. The HG exposure of MC caused substantial increases in connective tissue growth factor (CTGF) expression and collagen IV secretion with mesangial hyperplasia, which were repealed by adding PCA. PCA boosted HG-plummeted membrane type-1 matrix metalloproteinase expression and dampened HG-elevated tissue inhibitor of matrix metalloproteinase-2 expression through disturbing transforming growth factor β (TGF-β)-SMAD signaling, facilitating extracellular matrix degradation. This study further revealed that PCA ameliorated HG-inflamed mesangial inflammation accompanying induction of intracellular cell adhesion molecule-1 and monocyte chemoattractant protein-1 (MCP-1) responsible for CTGF expression. The induction of intracellular cell adhesion molecule-1 and MCP-1 was mediated via TGF-β signaling, which was suppressed by PCA. In addition, the HG-promoted CTGF expression entailed nuclear factor κB (NF-κB) signaling involved in MCP-1 transcription. The HG-TGF-β induction was blocked in the presence of a NF-κB inhibitor, and the nuclear NF-κB translocation was blunted by a TGF-β receptor 1 inhibitor. PCA dampened NF-κB translocation in HG-exposed MC. These results demonstrate that there was a crosstalk between TGF-β-SMAD and NF-κB pathways in the diabetes-associated mesangial fibrosis and inflammation, which appeared to be severed by PCA.
authors.affiliation: Department of Food and Nutrition and the Regional Research Universities Program/Medical & Bio-Materials Research Center, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kim
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
authors.forename: Jung-Lye
authors.initials: JL
authors.lastname: Kim
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000187:drug effects / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005355:Fibrosis; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D003313:Zea mays / Q000737:chemistry*
chemical_list: D000872:Anthocyanins; D024141:Collagen Type IV; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1; D055513:Connective Tissue Growth Factor; D020778:Matrix Metalloproteinase 2; D005947:Glucose