title: KIOM-79 prevents S100b-induced TGF-beta1 and fibronectin expression in mouse mesangial cells.
abstract: OBJECTIVE
  In this study, we investigated whether KIOM-79 inhibits transforming growth factor-beta 1 (TGF-beta1) and fibronectin expression in mouse mesangial cells cultured under S100b, a specific ligand of the receptor for advanced glycation end products (RAGE).
  
  
  METHODS
  Cell counting kit (CCK-8) assay was employed to evaluate the viability of KIOM-79-treated mesangial cells. The effect of KIOM-79 on S100b-induced TGF-beta1 and fibronectin expression was investigated using RT-PCR, ELISA, and Western blot on mesangial cells.
  
  
  RESULTS
  KIOM-79 (up to 50 microg/ml) appeared to have no effect on cell viability. S100b induced an increase in the expression TGF-beta1 and fibronectin. Expression of TGF-beta1 and fibronectin was inhibited significantly by KIOM-79 treatment in mesangial cells. KIOM-79 also inhibited the expression of NF-kB and inactivated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) 1/2 in mesangial cells. KIOM-79 pretreatment inhibited increased malondialdehyde (a product of lipid peroxidation and a marker for oxidative stress) levels in S100b-induced mesangial cells.
  
  
  CONCLUSIONS
  These data demonstrate that KIOM-79 inhibits expression of TGF-beta1 and fibronectin through inactivation of MAPK/ERK1/2 signaling, reduction in malondiadehyde levels, and inhibition of NF-kB in mesangial cells cultured under diabetic conditions. KIOM-79 could be beneficial for preventing of the development of diabetic complications such as nephropathy.
authors: Diabetic Complications Research Center, Division of Traditional Korean Medicine, Integrated Research, Korea Institute of Oriental Medicine, 483 Exporo, Yuseong-gu, Daejeon 305-811, Republic of Korea.
authors: Dong Ho
authors: DH
authors: Jung
authors: Young Sook
authors: YS
authors: Kim
authors: Jin Sook
authors: JS
authors: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D008315:Malondialdehyde / Q000037:antagonists & inhibitors; D050527:Mesangial Cells / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D009418:S100 Proteins / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D005353:Fibronectins; C517978:KIOM 79; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D009418:S100 Proteins; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases