Cadmium, vectorial active transport, and MT-3-dependent regulation of cadherin expression in human proximal tubular cells.
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.
Bathula
Chandra S
CS
Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58202, USA.
Garrett
Scott H
SH
Zhou
Xu Dong
XD
Sens
Mary Ann
MA
Sens
Donald A
DA
Somji
Seema
S
D001693:Biological Transport, Active / Q000187:drug effects; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D019187:Cadmium Compounds / Q000378:metabolism / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000473:pathology; D014162:Transfection
D015820:Cadherins; D019187:Cadmium Compounds; D020033:Protein Isoforms; D012333:RNA, Messenger; D008668:Metallothionein