J Korean Soc Transplant.  2005 Jun;19(1):8-13.

Effects of Tautomycetin on the Proliferation and Fibronectin Secretion in Vascular Smooth Muscle Cells and Glomerular Mesangial Cells

• Kim JH
• Lee TY
• Park J
• Ha H
• Kang SW
• Kim YS

Abstract

PURPOSE
Proliferation and extracellular matrix (ECM) accumulation in the vascular smooth muscle cell (VSMC) and glomerular mesangial cell (MC) play key roles in the development and the progression of transplant glomerulosclerosis and chronic allograft nephropathy. Tautomycetin (TMC), a newly developed immunosuppressive agent, induces T-lymphocyte apoptosis through the inhibition of tyrosine kinase and protein phosphatase 1. We examined the effects of TMC on platelet-derived growth factor (PDGF)-induced proliferation and ECM synthesis in cultured VSMCs and MCs of Sprague- Dawley rats, and investigated the molecular mechanisms that are involved.
METHODS
Different concentrations of TMC were administered 1 hour before the addition of PDGF 10 ng/mL into the growth-arrested and synchronized cells. Cell proliferation was assessed by methylthiazoletetrazolium (MTT) assay. Caspase-3 cleavage, fibronectin secretion, and the activation of Akt, ERK, and p38 MAPK were assessed by Western blot analysis, respectively.
RESULTS
PDGF 10 ng/ mL increased cell proliferation, fibronectin secretion, and the activation of Akt, ERK, and p38 MAPK in both VSMCs and MCs. In both cultured cells, TMC at above 1 microgram/mL significantly reduced basal MTT and increased cleavage caspase-3 in a dose-dependent manner. TMC at 100 ng/mL decreased the PDGF-induced VSMC and MC proliferation without cytotoxicity. However, fibronectin secretion and the activation of Akt, ERK, and p38 MAPK were not affected at this low concentration of TMC, respectively.
CONCLUSION
The present data demonstrated that low-dose TMC reduced PDGF-induced VSMC and MC proliferation without affecting the fibronectin secretion and cellular kinase activation.

Keyword

Tautomycetin; Vascular smooth muscle cell; Mesangial cell; Proliferation; Extracellular matrix

MeSH Terms

Allografts
Animals
Apoptosis
Blotting, Western
Caspase 3
Cell Proliferation
Cells, Cultured
Extracellular Matrix
Fibronectins*
Mesangial Cells*
Muscle, Smooth, Vascular*
p38 Mitogen-Activated Protein Kinases
Phosphotransferases
Platelet-Derived Growth Factor
Protein Phosphatase 1
Protein-Tyrosine Kinases
Rats
T-Lymphocytes
Caspase 3
Fibronectins
Phosphotransferases
Platelet-Derived Growth Factor
Protein Phosphatase 1
Protein-Tyrosine Kinases
p38 Mitogen-Activated Protein Kinases