Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process

Y. Xie, S. Nishi, S. Iguchi, N. Imai, M. Sakatsume, A. Saito, Mika Ikegame, N. Iino, H. Shimada, M. Ueno, H. Kawashima, M. Arakawa, F. Gejyo

Research output: Contribution to journalArticle

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Abstract

Background. There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There is little information on the expression and role of OPN in gentamicin-induced acute tubular necrosis (ATN) and its recovery process. Methods. A severe ATN model was made using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their relationships to each other were examined from the early tubular necrotic period to the late recovery period by Northern blotting, in situ hybridization, and double immunohistochemical staining. Results. In the gentamicin group, OPN mRNA and protein were expressed in only the PCNA-positive proliferating cortical distal tubules, not in the necrotic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules on days 10, 15, and 30. The localization of PCNA-positive cells was almost always accompanied with the up-regulated expression of OPN using quantitative analysis (P <0.01). CD44 expression was markedly up-regulated in the renal cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the experimental period. Conclusions. These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.

Original languageEnglish
Pages (from-to)959-974
Number of pages16
JournalKidney International
Volume59
Issue number3
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Osteopontin
Gentamicins
Necrosis
Nuclear Antigens
Low Density Lipoprotein Receptor-Related Protein-2
Kidney
Messenger RNA
Chemokines
Northern Blotting
In Situ Hybridization
Wistar Rats
Regeneration
Proteins
Epithelium
Epithelial Cells
Macrophages
Staining and Labeling
Control Groups
Water
Wounds and Injuries

Keywords

  • Acute renal failure
  • CD44
  • Cell proliferation
  • Macrophage
  • Megalin
  • Regeneration

ASJC Scopus subject areas

  • Nephrology

Cite this

Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process. / Xie, Y.; Nishi, S.; Iguchi, S.; Imai, N.; Sakatsume, M.; Saito, A.; Ikegame, Mika; Iino, N.; Shimada, H.; Ueno, M.; Kawashima, H.; Arakawa, M.; Gejyo, F.

In: Kidney International, Vol. 59, No. 3, 2001, p. 959-974.

Research output: Contribution to journalArticle

Xie, Y, Nishi, S, Iguchi, S, Imai, N, Sakatsume, M, Saito, A, Ikegame, M, Iino, N, Shimada, H, Ueno, M, Kawashima, H, Arakawa, M & Gejyo, F 2001, 'Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process', Kidney International, vol. 59, no. 3, pp. 959-974. https://doi.org/10.1046/j.1523-1755.2001.059003959.x
Xie, Y. ; Nishi, S. ; Iguchi, S. ; Imai, N. ; Sakatsume, M. ; Saito, A. ; Ikegame, Mika ; Iino, N. ; Shimada, H. ; Ueno, M. ; Kawashima, H. ; Arakawa, M. ; Gejyo, F. / Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process. In: Kidney International. 2001 ; Vol. 59, No. 3. pp. 959-974.
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abstract = "Background. There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There is little information on the expression and role of OPN in gentamicin-induced acute tubular necrosis (ATN) and its recovery process. Methods. A severe ATN model was made using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their relationships to each other were examined from the early tubular necrotic period to the late recovery period by Northern blotting, in situ hybridization, and double immunohistochemical staining. Results. In the gentamicin group, OPN mRNA and protein were expressed in only the PCNA-positive proliferating cortical distal tubules, not in the necrotic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules on days 10, 15, and 30. The localization of PCNA-positive cells was almost always accompanied with the up-regulated expression of OPN using quantitative analysis (P <0.01). CD44 expression was markedly up-regulated in the renal cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the experimental period. Conclusions. These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.",
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AU - Xie, Y.

AU - Nishi, S.

AU - Iguchi, S.

AU - Imai, N.

AU - Sakatsume, M.

AU - Saito, A.

AU - Ikegame, Mika

AU - Iino, N.

AU - Shimada, H.

AU - Ueno, M.

AU - Kawashima, H.

AU - Arakawa, M.

AU - Gejyo, F.

PY - 2001

Y1 - 2001

N2 - Background. There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There is little information on the expression and role of OPN in gentamicin-induced acute tubular necrosis (ATN) and its recovery process. Methods. A severe ATN model was made using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their relationships to each other were examined from the early tubular necrotic period to the late recovery period by Northern blotting, in situ hybridization, and double immunohistochemical staining. Results. In the gentamicin group, OPN mRNA and protein were expressed in only the PCNA-positive proliferating cortical distal tubules, not in the necrotic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules on days 10, 15, and 30. The localization of PCNA-positive cells was almost always accompanied with the up-regulated expression of OPN using quantitative analysis (P <0.01). CD44 expression was markedly up-regulated in the renal cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the experimental period. Conclusions. These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.

AB - Background. There is controversy regarding the exact localization and roles of osteopontin (OPN), a multipotential chemokine, in renal injury. There is little information on the expression and role of OPN in gentamicin-induced acute tubular necrosis (ATN) and its recovery process. Methods. A severe ATN model was made using male Wistar rats by injecting gentamicin (150 mg/kg/day) for five days and limiting the provision of water. The expression and localization of OPN mRNA and protein, ED1 as a macrophage marker, proliferating cellular nuclear antigen (PCNA), CD44 as an OPN receptor, megalin as a proximal tubule marker, and their relationships to each other were examined from the early tubular necrotic period to the late recovery period by Northern blotting, in situ hybridization, and double immunohistochemical staining. Results. In the gentamicin group, OPN mRNA and protein were expressed in only the PCNA-positive proliferating cortical distal tubules, not in the necrotic proximal tubules, until day 6 after the first administration, but were found markedly in PCNA-positive regenerative proximal and distal tubules on days 10, 15, and 30. The localization of PCNA-positive cells was almost always accompanied with the up-regulated expression of OPN using quantitative analysis (P <0.01). CD44 expression was markedly up-regulated in the renal cortical tubular epithelium from days 6 to 30. In the control group, no expression of OPN and CD44 in the cortical area was found throughout the experimental period. Conclusions. These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.

KW - Acute renal failure

KW - CD44

KW - Cell proliferation

KW - Macrophage

KW - Megalin

KW - Regeneration

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