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

Xie, Yuansheng; Nishi, Shinichi; Iguchi, Seitaro; Imai, Naofumi; Sakatsume, Minoru; Saito, Akihiko; Ikegame, Mika; Iino, Noriaki; Shimada, Hisaki; Ueno, Mitsuhiro; Kawashima, Hiroyuki; Arakawa, Masaaki; Gejyo, Fumitake

doi:10.1046/j.1523-1755.2001.059003959.x

Cited by 78 publications

(38 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As described previously [9], renal proximal tubular necrosis appeared to develop on day 6 (day 1–5 administration of gentamicin) in the gentamicin group. On day 10, there was a lot of desquamated epithelial cell debris in the dilated tubular lumens.…”

Section: Resultssupporting

confidence: 74%

“…Our previous study showed the up-regulated expression of CD44 in renal tubules during the recovery process after acute tubular necrosis (ATN) [9], but the exact localization and distribution of CD44 during the process of injury and repair of the kidneys remains poorly understood. In this study, we used a gentamicin-induced ATN and spontaneous recovery model in rats and two distinct antibodies, an anti-rat distal extracellular domain (OX49) of standard CD44 (CD44-OX49) and an anti-rat CD44 cytoplasmic tail (CD44CPT), surveyed the different localization of CD44-OX49 and CD44CPT in the surface membranes of renal tubular epithelial cells in different recovery stages after ATN and discussed the potential roles of CD44 localized on different surface membrane.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Different Type and Localization of CD44 on Surface Membrane of Regenerative Renal Tubular Epithelial Cells in vivo

et al. 2004

Self Cite

View full text Add to dashboard Cite

Background: CD44 is a transmembrane glycoprotein comprising an extracellular domain, a transmembrane domain, and a cytoplasmic tail. Previous studies demonstrated that CD44 was generally restricted to lateral-basal plasma membrane (PM) of epithelial cells, whether it localized on apical PM in vivo has not been clarified. Methods: In this study, we used a gentamicin-induced acute tubular necrosis (ATN) and spontaneous recovery model in rats and two distinct antibodies, an anti-rat distal extracellular domain (OX49) of standard CD44 (CD44-OX49) and an anti-rat CD44 cytoplasmic tail (CD44CPT), to survey the localization of CD44-OX49 and CD44CPT on the PM in renal tubular epithelial cells in different recovery stages after ATN with immunohistochemistry and immunoelectron-microscopic examinations. Results: CD44-OX49 was localized not only on the lateral-basal PM in tubular epithelial cells, but also on the apical surface membrane in PCNA-positive newly regenerative tubular epithelial cells in early recovery stages after ATN. However, CD44CPT was only localized on the lateral-basal PM. The immunoelectron-microscopic results showed that CD44-OX49 localization was changed from the apical to lateral to basal surface membrane in renal tubular epithelial cells during the recovery process after ATN, finally disappearing from basal PM when normal polarized epithelial cells formed. Conclusions: These results suggest that there were two types of CD44 including CD44 without a cytoplasmic tail localizing on the apical surface membrane related to newly regenerative epithelial cells, and CD44 with a cytoplasmic tail localizing on the lateral-basal PM related to establishment of tubular epithelial cell polarity after ATN in vivo.

show abstract

Section: Resultssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Different Type and Localization of CD44 on Surface Membrane of Regenerative Renal Tubular Epithelial Cells in vivo

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…In situ hybridization with rat SM22α cRNA was conducted as previously described [22]. For digoxigenin-labeled probe synthesis, in vitro transcription was performed using a Dig RNA labeling kit (SP6/T7; Roche).…”

Section: Methodsmentioning

confidence: 99%

SM22α: The Novel Phenotype Marker of Injured Glomerular Epithelial Cells in Anti-Glomerular Basement Membrane Nephritis

Ogawa

Sakatsume

Wang

et al. 2007

Nephron Exp Nephrol

Self Cite

View full text Add to dashboard Cite

Background/Aims: Our previous comprehensive analysis of the genes expressed in kidneys with anti-glomerular basement membrane (GBM) nephritis using DNA microarrays showed that SM22α was one of the highly expressed genes. SM22α is a 22-kDa cytoskeletal protein that is exclusively expressed in smooth muscle cells. We investigated the localization of SM22α at mRNA and protein levels, and its pathological significance in anti-GBM nephritis kidneys. Methods: Northern blot analysis, in situ hybridization, immunohistochemistry and double immunofluorescence studies were performed. The specific antibody (Ab) against SM22α was obtained by immunization of rabbits with recombinant rat SM22α protein. Results: SM22α mRNA expression was upregulated in kidneys and inducibly expressed in the parietal and visceral glomerular epithelial cells in anti-GBM nephritis kidneys. Immunohistochemistry with anti-SM22α Ab showed that SM22α protein was localized in the same series of cells. Double immunofluorescence with anti-SM22α and anti-glomerular cell markers demonstrated that SM22α might be expressed in epithelial cells of injured glomeruli. In visceral epithelial cells, SM22α might be expressed in cells in which podocyte specific markers, podocalyxin and nephrin were lost. Conclusion: The injured glomerular epithelial cells in anti-GBM nephritis might undergo structural and functional alterations, including the expression of a smooth muscle marker, SM22α.

show abstract

“…OPN, a secreted glycoprotein, has been demonstrated to be expressed in normal renal tissues, however, is induced in abnormal kidneys. Though a number of studies [19] have explored the role of OPN in renal diseases, direct evidence on its role in renal injury has not been described. Moreover, very little information is available on human renal disease states and the role of OPN in drug-induced nephrotoxicity in transplant patients.…”

Section: Discussionmentioning

confidence: 99%

“…In a number of experimental models, expression of OPN is highlighted in these cells. Xie et al [19] suggested that OPN was related to the proliferation and regeneration of tubular epithelial cells after tubular damage. Lewington et al [27] observed that OPN was expressed in regenerating tubules 3 days after induction of acute ischemic injury but not in sham-operated controls.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus and Cyclosporinein vitro and in vivo Induce Osteopontin mRNA and Protein Expression in Renal Tissues

Khanna¹

2005

Nephron Exp Nephrol

View full text Add to dashboard Cite

The mechanism of immunosuppression-linked nephrotoxicity in organ transplantation remains to be solved. Expression of osteopontin (OPN), a multifunctional secreted glycoprotein, has been associated with various forms of renal injuries. In this study, using in vitro and in vivo models, we examined the effects of cyclosporine (CsA) and tacrolimus (TAC) on OPN mRNA and protein expression. We also examined if CsA- and TAC-induced OPN expression is dependent on transforming growth factor (TGF)-β expression. For in vivo experiments mice and rats were injected with CsA (25 mg/kg) and TAC (0.2 mg/kg). For in vitro experiments, human proximal tubular epithelial (PTE) cells were treated with CsA and TAC for 4 h. To study the in vivo effect of TGF-β on OPN mRNA, mice were injected with recombinant TGF-β protein (3 mg/kg). The expression of OPN was also studied in CsA-treated PTE cells with and without anti-TGF-β antibody. At the end of in vitro and in vivo treatments, RNA was isolated from kidney tissue and renal cells reverse transcribed to cDNA and amplified for OPN mRNA. Using immunochemistry and Western blot analysis OPN protein expression was also studied in vivo and in vitro, respectively. Both in vitro and in vivo treatment with CsA and TAC resulted in significantly increased OPN mRNA and protein expression. TGF-β treatment in vivo also resulted in a significantly increased OPN mRNA expression and anti-TGF-β antibody but not the control antibody in vivo in CsA-treated mice, and in vitro in CsA-treated PTE cells inhibited OPN mRNA expression. OPN may contribute to the CsA- and TAC-induced nephrotoxicity in organ transplant recipients and the increased OPN expression might be mediated by TGF-β.

show abstract

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

Abstract: These results suggested that OPN is related to the proliferation and regeneration of tubular epithelial cells after tubular damage.

Cited by 78 publications

References 45 publications

Different Type and Localization of CD44 on Surface Membrane of Regenerative Renal Tubular Epithelial Cells in vivo

Different Type and Localization of CD44 on Surface Membrane of Regenerative Renal Tubular Epithelial Cells in vivo

SM22α: The Novel Phenotype Marker of Injured Glomerular Epithelial Cells in Anti-Glomerular Basement Membrane Nephritis

Tacrolimus and Cyclosporinein vitro and in vivo Induce Osteopontin mRNA and Protein Expression in Renal Tissues

Contact Info

Product

Resources

About