title: Expression of the heat shock protein 47 in gentamicin-treated rat kidneys.
abstract: Heat-shock proteins (HSPs) are rapidly synthesized in cells in response to various cytotoxic agents. Although several stress proteins are actively involved in the gentamicin-induced renal damages, the possible role of HSP47 in this condition is not yet clear. In this study, the expression of HSP47 in the gentamicin nephrotoxicity was examined by immunohistochemistry. Twenty male Wistar rats were sacrificed at day 0, 3, 7, 14 and 28 after subcutaneous injection of gentamicin. Gentamicin treatment causes tubular necrosis at day 3, followed by tubular regenerative changes and interstitial fibrosis, which was most prominent at day 14. The renal structures returned to almost normal architectures at day 28. By immunohistochemistry, HSP47 was weakly expressed in most of the glomeruli and occasionally in interstitial cells in the control rat kidneys. In contrast, strong immunostaining for HSP47 was noted in the tubular epithelial cells and interstitial cells in gentamicin treated rat kidneys, and strongest staining was observed at day 7. The immunostaining for HSP47 then gradually decreased, and returned to the normal level at day 28. In the whole experimental period staining pattern of HSP47 in the glomeruli was not changed. In addition, phenotypically altered tubulointerstitial cells including regenerative tubular epithelial cells (immuno-positive for vimentin) and interstitial cells (immuno-positive for alpha-smooth muscle actin) were found in gentamicin nephrotoxicity. Expression of type III collagen increased in the areas of interstitial fibrosis. By double immunostaining, the regenerated and phenotypically altered tubulointerstitial cells were found to express HSP47 in and around interstitial fibrosis. It is concluded that overexpression of HSP47 by phenotypically altered renal cells might play a significant role in the development of gentamicin nephrotoxicity.
authors.affiliation: Second Department of Pathology, Nagasaki University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Cheng
authors.forename: M S
authors.initials: MS
authors.lastname: Razzaque
authors.forename: A
authors.initials: A
authors.lastname: Nazneen
authors.forename: T
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005839:Gentamicins / Q000009:adverse effects*; D050958:HSP47 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014746:Vimentin / Q000378:metabolism
chemical_list: D000199:Actins; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D050958:HSP47 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494662:Serpinh1 protein, rat; D014746:Vimentin; D003094:Collagen