EGF and EGF‐receptor expression in rat anti‐Thy‐1 mesangial proliferative nephritis

David J. NIKOLIC‐PATERSON, Gregory H. TESCH, Hui Y. LAN, Kiyotaka NUKII, Rita FOTI, Robert C. ATKINS

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4 Citations (Scopus)

Abstract

Summary: Epidermal growth factor (EGF) is a potent mesangial cell and tubular epithelial cell mitogen. Based upon the novel finding that rat mesangial cells express EGF mRNA and protein in vitro, we investigated whether renal EGF production was involved in mesangial proliferation and concomitant tubular epithelial proliferation in rat anti‐Thy‐1 mesangial proliferative nephritis. During the period of mesangial proliferation in anti‐Thy‐1 nephritis (days 4–14) no EGF immunoreactive material was detected within the glomerulus. Epidermal growth factor‐receptor (EGF‐R) expression, which is strong on podocytes in normal glomeruli, was notably absent from focal areas of proliferating mesangial cells, suggesting that EGF available from the circulation was not involved in mesangial cell proliferation. Concomitant with the transient decline in creatinine clearance on day 8 of disease, there was mild tubular injury and a significant increase in cortical tubular proliferation as assessed by expression of the proliferating cell nuclear antigen (PCNA). Double immunohistochemistry staining found that the increased cortical tubular proliferation on day 8 occurred in EGF tubules, but not EGF+ tubules. In contrast, there was an increase in proliferation of EGF+ tubules, but not EGF tubules, on day 28. Renal EGF mRNA and protein expression was down‐regulated over days 1‐14, with a rebound in expression on day 28 which correlated with proliferation of EGF+ tubules. Tubular EGF‐R expression, which is most clearly seen on EGF+ tubules in normal rat kidney, was unchanged over the disease course. the potential role of EGF in tubular proliferation in normal and diseased states is discussed. In summary, this study finds no evidence to implicate EGF in mesangial cell proliferation in rat anti‐Thy‐1 nephritis, even though mesangial cells can express EGF in vitro, and suggests that EGF may regulate proliferation of tubular epithelial cells in different stages of disease.

Original languageEnglish
Pages (from-to)83-93
Number of pages11
JournalNephrology
Volume1
Issue number1
DOIs
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Keywords

  • anti‐Thy‐1 nephritis
  • immunohistochemistry
  • mesangial cell
  • messenger RNA
  • proliferation
  • tubular epithelial cells

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