title: Hexavalent chromium induces expression of mesenchymal and stem cell markers in renal epithelial cells.
abstract: Cr(VI) causes severe kidney damage. The patient's renal function could gradually recover by spontaneous kidney regeneration. The molecular effect of Cr(VI) on recovery of kidney cells, however, has not been clearly elucidated. Here we show that Cr(VI) induces expression of mesenchymal and stem cell markers, cell markers, such as paxillin, vimentin, α-SMA, nanog, and CD133 of HK-2 cells. Moreover, Cr(VI) activates epithelial-to-mesenchymal transition (EMT). By revealing that levels of dihydrodiol dehydrogenase were promptly reduced following Cr(VI) challenge, our data suggested that DDH could be involved in a Cr(VI)-related oxidation to generate massive reactive oxygen species and H2 O2 , and to create intracellular hypoxia, which then increased levels of SUMO-1 activating enzyme subunit 2, and sumoylation of eukaryotic elongation factor-2, to mediate the subsequent molecular and cellular responses, e.g., expression of mesenchymal and stem cell markers. Pretreatment with vitamin C reduced Cr(VI)-related cellular effects. However, no evident effect was observed when vitamin C was added following Cr(VI) challenge.
authors.affiliation: Department of Health Beauty, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Li
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Cheng-Lin
authors.initials: CL
authors.lastname: Yang
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Kuan-Chih
authors.initials: KC
authors.lastname: Chow
authors.affiliation: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ting-Wei
authors.initials: TW
authors.lastname: Kuo
mesh_terms: D000071916:AC133 Antigen; D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002857:Chromium / Q000009:adverse effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D010088:Oxidoreductases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C000606023:PROM1 protein, human; D010455:Peptides; D014746:Vimentin; D002857:Chromium; C074702:chromium hexavalent ion; D010088:Oxidoreductases; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; D001205:Ascorbic Acid
keywords: CD133; Cr(VI); DDH; EMT; connexin-43; nanog; paxillin; vimentin