title: Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.
abstract: BACKGROUND
  Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated.
  
  
  METHODS
  Urinary levels of col(IV)alpha1, col(IV)alpha3 and col(IV)alpha5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)alpha chains, from col(IV)alpha1 to col(IV)alpha5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls.
  
  
  RESULTS
  Urinary levels of col(IV)alpha1, col(IV)alpha3, col(IV)alpha5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)alpha1 and col(IV)alpha3 urinary excretion correlated with the degree of chronic histological damage [col(IV)alpha1 R = 0.44, p < 0.001; col(IV)alpha3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)alpha5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)alpha3, col(IV)alpha4 and col(IV)alpha5 chains [p < 0.01 for all].
  
  
  CONCLUSIONS
  Patients with chronic acquired glomerulopathies show important alterations in the col(IV)alpha chain network mimicking some molecular features of the X-linked Alport's syndrome. Further studies are needed to show whether urinary levels of the col(IV)alpha chains may be used as markers for monitoring renal injury.
authors.affiliation: Department of Clinical Medicine, Nephrology and Health Science, University of Parma, Parma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Carnevali
authors.forename: Davide
authors.initials: D
authors.lastname: Martorana
authors.forename: Paolo
authors.initials: P
authors.lastname: Cravedi
authors.forename: Umberto
authors.initials: U
authors.lastname: Maggiore
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.forename: Achiropita
authors.initials: A
authors.lastname: Bovino
authors.forename: Silvia
authors.initials: S
authors.lastname: Mattei
authors.forename: Guido
authors.initials: G
authors.lastname: Orlandini
authors.forename: Rita
authors.initials: R
authors.lastname: Gatti
authors.forename: Mario
authors.initials: M
authors.lastname: Savi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Tauro M
authors.initials: TM
authors.lastname: Neri
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D024141:Collagen Type IV / Q000096:biosynthesis* / Q000652:urine; D005260:Female; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011487:Protein Conformation; D011507:Proteinuria; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D024141:Collagen Type IV; D012333:RNA, Messenger