title: Fractalkine increases mesangial cell proliferation through reactive oxygen species and mitogen-activated protein kinases.
abstract: Mesangial cell proliferation is one of the main features of chronic renal allograft rejection. One unique feature of fractalkine (CX3CL1) is its existence as both a membrane-tethered and a soluble form. Fractalkine expression is increased in acute and chronic allograft rejection. However, its role in mesangial cell proliferation has not yet been clearly explored. Thus, the present study examined whether fractalkine induced mesangial cell proliferation through production of reactive oxygen species (ROS) and activation of mitogen-activated protein kinase (MAPK), two known mediators of mesangial cell proliferation. Growth-arrested and synchronized mouse mesangial cells were stimulated with fractalkine in the presence versus absence of inhibitors against ROS, extracellular signal-regulated protein kinase (ERK), and p38 MAPK. Cell proliferation was assessed by methylthiazoletetrazolium assay, dichlorofluorescein (DCF)-sensitive cellular ROS production by a fluorometer, and MAPK activation by Western blot analysis. Fractalkine (10-50 ng/mL) significantly increased mesangial cell proliferation at 24 hours in a dose-dependent manner, an effect that was abrogated by the ROS and MAPK inhibitors. Fractalkine (50 ng/mL) also induced cellular ROS production and activation of ERK1/2 and p38 MAPK in mesangial cells. These results demonstrated that fractalkine can induce mesangial cell proliferation through production of cellular ROS and activation of MAPK.
authors.affiliation: Department of Bioinspired Science and Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: K H
authors.initials: KH
authors.lastname: Song
authors.forename: H
authors.initials: H
authors.lastname: Ha
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005470:Fluorometry; D020935:MAP Kinase Signaling System / Q000187:drug effects; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases