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Epidemiological studies implicate arsenic exposure to CKD, but the role of arsenic in kidney fibrosis and the underlying mechanism is still unclear. It is in this context that the current study evaluated the effects of long\u2010term arsenic exposure on the cellular response in morphology, and marker genes expression with respect to fibrosis using human kidney 2 (HK\u20102) epithelial cells. Results of this study revealed that in addition to increased growth, HK\u20102 cells underwent phenotypic, biochemical and molecular changes indicative of epithelial\u2013mesenchymal transition (EMT) in response to the exposure to arsenic. Most importantly, the arsenic\u2010exposed cells acquired the pathogenic features of fibrosis as supported by increased expression of markers for fibrosis, such as Collagen I, Fibronectin, transforming growth factor \u03b2, and \u03b1\u2010smooth muscle actin. Upregulation of fibrosis associated signaling molecules such as tissue inhibitor of metalloproteinases\u20103 and matrix metalloproteinase\u20102 as well as activation of AKT was also observed. Additionally, the expression of epigenetic genes (DNA methyltransferases 3a and 3b; methyl\u2010CpG binding domain 4) was increased in arsenic\u2010exposed cells. Treatment with DNA methylation inhibitor 5\u2010Aza\u20102\u2032\u2010dC reversed the EMT properties and restored the level of phospho\u2010AKT. Together, these data for the first time suggest that long\u2010term exposure to arsenic can increase the risk of kidney fibrosis. Additionally, our data suggest that the arsenic\u2010induced fibrotic changes are, at least in part, mediated by DNA methylation and therefore potentially can be reversed by epigenetic therapeutics.<\/jats:p>","DOI":"10.1002\/jcp.27244","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T13:25:38Z","timestamp":1536326738000},"page":"4713-4725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Arsenic induces fibrogenic changes in human kidney epithelial cells potentially through epigenetic alterations in DNA methylation"],"prefix":"10.1002","volume":"234","author":[{"given":"Yu\u2010Wei","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Environmental Toxicology The Institute of Environmental and Human Health, Texas Tech University Lubbock 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