title: New role of the human equilibrative nucleoside transporter 1 (hENT1) in epithelial-to-mesenchymal transition in renal tubular cells.
abstract: Epithelial-to-mesenchymal transition (EMT) is an important pro-fibrotic event in which tubular epithelial cells are transformed into myofibroblasts. Nucleoside transporters (NT) are regulated by many factors and processes, some of which are involved in fibrosis, such as cytokines, inflammation, and proliferation. Equilibrative nucleoside transporter 1 (ENT1) has been proved to be the most widely expressed adenosine transporter. In that sense, ENT1 may be a key player in cell damage signaling. Here we analyze the role of human ENT1 (hENT1) in the EMT process in proximal tubular cells. Addition of the main inducer of EMT, the transforming growth factor-β1, to HK-2 cells increased hENT1 mRNA and protein level expression. ENT1-mediated adenosine uptake was also enhanced. When cells were incubated with dipyridamole to evaluate the potential contribution of ENT1 to EMT by blocking its transport activity, EMT was induced. Moreover, the knock down of hENT1 with siRNA induced EMT and collagen production in HK-2 cells. Kidneys isolated from ENT1 knockout mice showed higher levels of interstitial collagen and α-SMA positive cells than wild-type mice. Our results point to a new potential role of hENT1 as a modulator of EMT in proximal tubular cells. In this sense, hENT1 could be involved in renal protection processes, and the loss or reduced expression of hENT1 would lead to an increased vulnerability of cells to the onset and/or progression of renal fibrosis.
authors.affiliation: Laboratori de Biologia Molecular, Universitat Autònoma de Barcelona, Fundació Puigvert, REDinREN, Institut Investigació Biosanitaria Sant Pau, Barcelona, Catalonia, Spain. eguillen@fundacio-puigvert.es
authors.forename: Elena
authors.initials: E
authors.lastname: Guillén-Gómez
authors.forename: Itziar
authors.initials: I
authors.lastname: Pinilla-Macua
authors.forename: Sandra
authors.initials: S
authors.lastname: Pérez-Torras
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Arce
authors.forename: José A
authors.initials: JA
authors.lastname: Ballarín
authors.forename: Marçal
authors.initials: M
authors.lastname: Pastor-Anglada
authors.forename: Montserrat M
authors.initials: MM
authors.lastname: Díaz-Encarnación
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D033721:Equilibrative Nucleoside Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D033721:Equilibrative Nucleoside Transporter 1; D034741:RNA, Small Interfering; C438649:SLC29A1 protein, human; C498476:SLC29A1 protein, mouse; D053773:Transforming Growth Factor beta1; D003094:Collagen; D000241:Adenosine