KIOM-79 prevents S100b-induced TGF-beta1 and fibronectin expression in mouse mesangial cells.

Abstract

AIM OF THE STUDY:

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).

MATERIALS AND 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: Dong Ho Jung, Young Sook Kim, Jin Sook Kim
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 125 Issue 3 Pg. 374-9 (Sep 25 2009) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 19666101 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibronectins
• KIOM 79
• NF-kappa B
• Plant Extracts
• RNA, Messenger
• S100 Proteins
• Transforming Growth Factor beta1
• Malondialdehyde
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Cell Line
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Fibronectins (genetics, metabolism)
• Malondialdehyde (antagonists & inhibitors)
• Mesangial Cells (metabolism)
• Mice
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors)
• NF-kappa B (antagonists & inhibitors)
• Phosphorylation (drug effects)
• Plant Extracts (pharmacology)
• RNA, Messenger (metabolism)
• S100 Proteins (pharmacology)
• Time Factors
• Transforming Growth Factor beta1 (metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)