Heparin-binding EGF-like growth factor is expressed by mesangial cells and is involved in mesangial proliferation in glomerulonephritis.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a new member of the EGF family, is mitogenic for several types of cells, through binding to cell surface heparan sulphate proteoglycans. This study has attempted to delineate HB-EGF expression by mesangial cells and to identify its role in experimental and human glomerulonephritis. Rat mesangial cells, cultured in the presence of phorbol acetate, hydrogen peroxide, interleukin-1beta, and tumour necrosis factor-alpha, expressed HB-EGF mRNA. Recombinant HB-EGF stimulated rat mesangial cells to proliferate and to express types I and III collagen. In the rat anti-Thy-1.1 nephritis, glomerular HB-EGF mRNA was up-regulated and peaked at days 5-7; its expression at the protein level in the glomerulus was prominent at days 5-10. By immunofluorescence, HB-EGF was positive predominantly in the mesangial area of renal tissues from 23 of 45 patients with various types of human glomerulonephritis, showing a significant correlation with the grade of mesangial proliferation; there was no staining in tissues from patients with minimal change nephrotic syndrome and normal kidney tissues. These data provide the evidence that HB-EGF is synthesized and expressed by mesangial cells and stimulates mesangial cell proliferation and collagen synthesis in vitro. HB-EGF is a potential mediator in mesangial cell proliferation and matrix expansion in experimental and human glomerulonephritis.
Takemura
T
T
Department of Pediatrics, Kinki University School of Medicine 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
Murata
Y
Y
Hino
S
S
Okada
M
M
Yanagida
H
H
Ikeda
M
M
Yoshioka
K
K
D000818:Animals; D018929:Cell Culture Techniques; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007518:Isoantibodies; D012333:RNA, Messenger; C035678:anti-Thy antibody; D004815:Epidermal Growth Factor; D003094:Collagen; D004247:DNA