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Heparin‐binding EGF‐like growth factor is expressed by mesangial cells and is involved in mesangial proliferation in glomerulonephritis
Author(s) -
Takemura Tsukasa,
Murata Yuka,
Hino Satoshi,
Okada Mitsuru,
Yanagida Hidehiko,
Ikeda Masaru,
Yoshioka Kazuo
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199911)189:3<431::aid-path460>3.0.co;2-i
Subject(s) - mesangial cell , mesangial proliferative glomerulonephritis , heparin binding egf like growth factor , epidermal growth factor , glomerulonephritis , medicine , endocrinology , growth factor , renal glomerulus , biology , chemistry , kidney , receptor
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‐1β, and tumour necrosis factor‐α, 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. Copyright © 1999 John Wiley & Sons, Ltd.