Regulation of heparin binding-epidermal growth factor like growth factor gene expression by LDL and oxidized-LDL in rat mesangial cells.
The present study was to determine whether low-density lipoprotein (LDL) and oxidized LDL (Ox-LDL) modulate the heparin binding-epidermal growth factor like growth factor (HB-EGF) gene expression in rat mesangial cells (RMC). Using Northern blot analysis, LDL and Ox-LDL stimulated the expression of RMC HB-EGF mRNA in a time- and concentration-dependent manner, and the stimulatory effect of Ox-LDL lasted longer than LDL. In addition, a protein kinase C (PKC) inhibitor-staurosporine and a PKC-depletion condition abolished both of the stimulatory activities of LDL and Ox-LDL, while H-8 (a protein kinase A inhibitor) and cAMP-antagonist (cyclic adenosine-3':5'-monophosphothioate) had little effect. Our data indicate that LDL and Ox-LDL enhance HB-EGF gene expression and both via the PKC pathway in RMC. As HB-EGF is a mitogen for RMC, our results suggest that lipoproteins may regulate RMC function by inducing HB-EGF gene expression and thus contribute to glomerular injury.
Tan
M S
MS
Graduate Institute of Medicine, Kaohsiung Medical College, Taiwan, Republic of China.
Lee
Y J
YJ
Shin
S J
SJ
Tsai
J H
JH
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D006493:Heparin; D011494:Protein Kinases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate