Induction of heparin-binding epidermal growth factor-like growth factor mRNA by protein kinase C activators.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent smooth muscle cell mitogen of macrophage origin. To determine whether the HB-EGF gene is transcribed and regulated in mesangial cells, we measured HB-EGF mRNA levels in cultured rat mesangial cells by RNA blot analysis. A 2.5-kb HB-EGF mRNA was detected in unstimulated mesangial cells. The protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) increased HB-EGF mRNA levels by 15-fold in mesangial cells, and this induction of HB-EGF mRNA by TPA was both time- and dose-dependent. HB-EGF mRNA could also be stimulated by 10% fetal calf serum, ionomycin, thrombin, and endothelin-1. Staurosporine, a protein kinase C inhibitor, abolished the induction of HB-EGF mRNA by TPA and serum. To determine whether HB-EGF is mitogenic for mesangial cells, we transfected COS cells with HB-EGF expression plasmids. Culture medium from COS cells transfected with these plasmids increased 3H-thymidine incorporation in mesangial cells in a dose-dependent manner. To our knowledge, this is the first report that HB-EGF is expressed in renal cells. This inducible transcription of HB-EGF suggests that it may have an autocrine role in mesangial cell proliferation in kidney disease.
Tan
M S
MS
Department of Biology, Kaohsiung Medical College, Taiwan, Republic of China.
Tsai
J C
JC
Lee
Y J
YJ
Chen
H C
HC
Shin
S J
SJ
Lai
Y H
YH
Perrella
M A
MA
Bianchi
C
C
Higashiyama
S
S
Endege
W
W
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
D000470:Alkaloids; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004247:DNA; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate