Cell Biology – Immunology – Pathology
Kidney International (2001) 59, 959–974; doi:10.1046/j.1523-1755.2001.059003959.x
Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process
Yuansheng Xie, Shinichi Nishi, Seitaro Iguchi, Naofumi Imai, Minoru Sakatsume, Akihiko Saito, Mika Ikegame, Noriaki Iino, Hisaki Shimada, Mitsuhiro Ueno, Hiroyuki Kawashima, Masaaki Arakawa and Fumitake Gejyo
Department of Nephrology, Guangxi Zhuang Autonomous Region Nan Xi Shan Hospital, Guilin, China; Department of Medicine II, Niigata University School of Medicine, First Department of Oral Anatomy and Department of Pharmacology, Niigata University, Faculty of Dentistry, Niigata, Japan
Correspondence: Shinichi Nishi, M.D., Department of Medicine (II), Niigata University School of Medicine, 1-757 Asahimachi-dori, Niigata 951-8510, Japan. E-mail: snishi@med.niigata-u.ac.jp
Received 29 March 2000; Revised 14 August 2000; Accepted 27 September 2000.
Abstract
Expression of osteopontin in gentamicin-induced acute tubular necrosis and its recovery process.
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.
Keywords:
acute renal failure, megalin, cell proliferation, regeneration, macrophage, CD44
