title: Palladin is upregulated in kidney disease and contributes to epithelial cell migration after injury.
abstract: Recovery from acute kidney injury involving tubular epithelial cells requires proliferation and migration of healthy cells to the area of injury. In this study, we show that palladin, a previously characterized cytoskeletal protein, is upregulated in injured tubules and suggest that one of its functions during repair is to facilitate migration of remaining cells to the affected site. In a mouse model of anti-neutrophilic cytoplasmic antibody involving both tubular and glomerular disease, palladin is upregulated in injured tubular cells, crescents and capillary cells with angiitis. In human biopsies of kidneys from patients with other kidney diseases, palladin is also upregulated in crescents and injured tubules. In LLC-PK1 cells, a porcine proximal tubule cell line, stress induced by transforming growth factor-β1 (TGF-β1) leads to palladin upregulation. Knockdown of palladin in LLC-PK1 does not disrupt cell morphology but does lead to a defect in cell migration. Furthermore, TGF-β1 induced increase in the 75 kDa palladin isoform occurs in both the nucleus and the cytoplasm. These data suggest that palladin expression is induced in injured cells and contributes to proper migration of cells in proximal tubules, possibly by regulation of gene expression as part of the healing process after acute injury.
authors.affiliation: 1] UNC Kidney Center, Chapel Hill, NC [2] UNC Department of Cell Biology and Physiology, Chapel Hill, NC.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Chang
authors.affiliation: UNC Department of Pathology and Laboratory Medicine, Chapel Hill, NC.
authors.forename: Adil H
authors.initials: AH
authors.lastname: Gasim
authors.affiliation: UNC Department of Cell Biology and Physiology, Chapel Hill, NC.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kerber
authors.affiliation: UNC Department of Cell Biology and Physiology, Chapel Hill, NC.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Patel
authors.affiliation: UNC Department of Cell Biology and Physiology, Chapel Hill, NC.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Glaubiger
authors.affiliation: UNC Kidney Center, Chapel Hill, NC.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Falk
authors.affiliation: 1] UNC Kidney Center, Chapel Hill, NC [2] UNC Department of Pathology and Laboratory Medicine, Chapel Hill, NC.
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.affiliation: UNC Department of Cell Biology and Physiology, Chapel Hill, NC.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Otey
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D003598:Cytoskeletal Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1