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.

We describe a patient with IgA nephropathy associated with Crohn disease. IgA nephropathy first appeared at the age of 10 years. Combined therapy with prednisolone, cyclophosphamide, warfarin, and angiotensin-converting enzyme inhibitor resulted in clinical improvement over the following year, and remission was maintained. At the age of 13 years, the patient developed Crohn disease and IgA nephropathy recurred. Significant increases in serum IgA were associated with progression of Crohn disease. An elemental diet combined with oral prednisolone resulted in clinical improvement of Crohn disease and in remission of nephropathy and normalization of serum IgA concentration. The clinical course of the two diseases was linked, suggesting a common pathogenetic mechanism involving an IgA immune response to mucosal challenge in the intestine.

These results indicate that membrane-bound HB-EGF can mediate both epithelial cell branching and cell motility. Localization of proHB-EGF to the site of cell-cell contact and development of tubule-like structures in collagen gels suggests that proHB-EGF may be an important morphogen for renal epithelial cells.

Coexpression of proHB-EGF and CD9 may render the renal epithelial cells more resistant to disruption of cell-cell and cell-matrix interactions and could accelerate the re-establishment of these attachments.

These findings indicate that the cell proliferation process precedes the evolution of diabetic glomerulopathy. The responses of OLETF MCs to n-LDL/ox-LDL and Ang II differed depending on the stage of diabetes. In the early phase, MCs were prone to proliferate, whereas in the late stage, MCs, which expressed higher levels of TGF-beta, tended to synthesize ECM. A functional switch in MCs may contribute to the development of glomerulosclerosis in diabetic nephropathy.