title: Periostin: novel tissue and urinary biomarker of progressive renal injury induces a coordinated mesenchymal phenotype in tubular cells.
abstract: BACKGROUND
  Periostin acts as an adhesion molecule during bone formation. Knowledge of its expression in kidney injury is scant.
  
  
  METHODS
  We investigated periostin function and expression in vivo in Sprague-Dawley rats after 5/6 nephrectomy (Nx), in DBA2J mice with streptozotocin-induced diabetic nephropathy (SZ-DN) and unilateral ureteral obstruction (UUO) and in vitro in mouse distal collecting tubular cells (MDCT) and in tissue and urine from chronic kidney disease (CKD) patients.
  
  
  RESULTS
  Periostin messenger RNA was increased after 5/6Nx and SZ-DN demonstrating generalizability of the increment in renal injury. Periostin was expressed predominantly in distal tubule (DT) epithelial cell cytoplasm in situ, in cells shed into the lumen, and, in lesser abundance, in glomeruli undergoing obsolescence, arterioles and in the tubulointerstitium in extracellular and intracellular locations. In affected DT after 5/6Nx, periostin expression appeared de novo, E-cadherin became undetectable and tubule cells displayed the mesenchymal marker proteins fibroblast-specific protein-1 (FSP1) and matrix metalloproteinase-9 (MMP9). Periostin overexpression in cultured MDCT cells dramatically induced MMP9 and FSP1 protein and suppressed E-cadherin. Periostin short interfering RNA blocked these changes. Urine periostin excretion increased over time after 5/6Nx, and it was also excreted in the urine of CKD patients. Urine periostin enzyme-linked immunosorbent assay at a cutoff of 32.66 pg/mg creatinine demonstrated sensitivity and specificity for distinguishing patients with CKD from healthy people (92.3 and 95.0%, respectively) comparing favorably with urine neutrophil gelatinase-associated lipocalin.
  
  
  CONCLUSIONS
  These data demonstrate that periostin is a mediator and marker of tubular dedifferentiation and a promising tissue and urine biomarker for kidney injury in experimental models and in clinical renal disease.
authors.affiliation: Los Angeles Biomedical Research Institute, Harbor-UCLA, Torrance, CA, USA.
authors.forename: Bancha
authors.initials: B
authors.lastname: Satirapoj
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Mina P
authors.initials: MP
authors.lastname: Chamberlin
authors.forename: Tiane
authors.initials: T
authors.lastname: Dai
authors.forename: Janine
authors.initials: J
authors.lastname: LaPage
authors.forename: Lynetta
authors.initials: L
authors.lastname: Phillips
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Nast
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Adler
mesh_terms: D000375:Aging; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008811:Mice, Inbred DBA; D009392:Nephrectomy; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014517:Ureteral Obstruction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C082838:Postn protein, mouse; C512836:Postn protein, rat; D012333:RNA, Messenger