KIOM-79 prevents S100b-induced TGF-beta1 and fibronectin expression in mouse mesangial cells.
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.
Jung
Dong Ho
DH
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.
Kim
Young Sook
YS
Kim
Jin Sook
JS
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
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