title: Periostin is induced in glomerular injury and expressed de novo in interstitial renal fibrosis.
abstract: Matricellular proteins participate in the pathogenesis of chronic kidney diseases. We analyzed glomerular gene expression profiles from patients with proteinuric diseases to identify matricellular proteins contributing to the progression of human nephropathies. Several genes encoding matricellular proteins, such as SPARC, THBS1, and CTGF, were induced in progressive nephropathies, but not in nonprogressive minimal-change disease. Periostin showed the highest induction, and its transcript levels correlated negatively with glomerular filtration rate in both glomerular and tubulointerstitial specimen. In well-preserved renal tissue, periostin localized to the glomerular tuft, the vascular pole, and along Bowman's capsule; no signal was detected in the tubulointerstitial compartment. Biopsies from patients with glomerulopathies and renal dysfunction showed enhanced periostin expression in the mesangium, tubular interstitium, and sites of fibrosis. Periostin staining correlated negatively with renal function. α-smooth muscle actin-positive mesangial and interstitial cells localized close to periostin-positive sites, as indicated by co-immunofluorescence. In vitro stimulation of mesangial cells by external addition of TGF-β1 resulted in robust induction of periostin. Addition of periostin to mesangial cells induced cell proliferation and decreased the number of cells expressing activated caspase-3, a marker of apoptosis. These human data indicate for the first time a role of periostin in glomerular and interstitial injury in acquired nephropathies.
authors.affiliation: Institute of Physiology and Division of Nephrology, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Kontheari
authors.initials: K
authors.lastname: Sen
authors.forename: Maja T
authors.initials: MT
authors.lastname: Lindenmeyer
authors.forename: Ariana
authors.initials: A
authors.lastname: Gaspert
authors.forename: Felix
authors.initials: F
authors.lastname: Eichinger
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Neusser
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000235:genetics; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport; D011507:Proteinuria / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014021:Tissue Preservation; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human