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Cadmium, vectorial active transport, and MT-3-dependent regulation of cadherin expression in human proximal tubular cells.
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2008 Apr; Vol. 102 (2), pp. 310-8. Date of Electronic Publication: 2008 Jan 08. - Publication Year :
- 2008
-
Abstract
- Previous studies from this laboratory have implicated the expression of the third isoform of metallothionein (MT-3) in the maintenance of proximal tubular vectorial active ion transport. It was shown that HK-2 cells have no expression of MT-3 and do not form domes in culture; whereas, the human proximal tubular (HPT) cells and HK-2 cells stably transfected with MT-3 [HK-2(MT-3)] form these structures. In the present study, this association was further explored by determining the effect of MT-3 expression on the expression of the E -, P -, N -, K -, and Ksp-cadherins. It was demonstrated that the HPT cells and HK-2(MT-3) cells had significant elevations in the expression of messenger RNA and protein for the E -, P -, and Ksp-cadherins compared with that of the HK-2 cells transfected with the blank vector [HK-2(blank vector)]. In contrast, the HK-2(blank vector) cells had significantly elevated expression of N- and K-cadherin compared with both the HPT and HK-2(MT-3) cell lines. These patterns of cadherin expression provide strong evidence that MT-3 might be involved in epithelial to mesenchymal transition that is postulated to occur during several disease states and in the mesenchymal to epithelial transition that occurs during normal kidney morphogenesis. A final goal of the study was to determine if Cd(+2) exposure influenced vectorial active transport of the proximal tubular cells and if this might occur through alterations in the expression of MT-3. It was shown that exposure to Cd(+2) eliminated vectorial active transport by the proximal tubular cell lines, but that Cd(+2) exposure did not reduce the expression of the MT-3 protein. The study shows that the level of MT-3 expression in HPT cells influences transepithelial resistance and cadherin expression but does not influence the Cd(+2)-induced loss of vectorial active transport.
- Subjects :
- Biological Transport, Active drug effects
Cadherins genetics
Cadmium Compounds metabolism
Cell Differentiation drug effects
Cell Line
Dose-Response Relationship, Drug
Electric Impedance
Epithelial Cells pathology
Epithelial Cells physiology
Gene Expression drug effects
Gene Expression Regulation drug effects
Humans
Kidney Tubules, Proximal metabolism
Kidney Tubules, Proximal pathology
Metallothionein genetics
Protein Isoforms genetics
Protein Isoforms metabolism
RNA, Messenger metabolism
Tight Junctions drug effects
Tight Junctions pathology
Transfection
Cadherins metabolism
Cadmium Compounds toxicity
Epithelial Cells drug effects
Kidney Tubules, Proximal drug effects
Metallothionein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0929
- Volume :
- 102
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 18182399
- Full Text :
- https://doi.org/10.1093/toxsci/kfn004