Alterations of type IV collagen alpha chains in patients with chronic acquired glomerulopathies: mRNA levels, protein expression and urinary loss.
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.
Sanna-Cherchi
Simone
S
Department of Clinical Medicine, Nephrology and Health Science, University of Parma, Parma, Italy.
Carnevali
Maria Luisa
ML
Martorana
Davide
D
Cravedi
Paolo
P
Maggiore
Umberto
U
Alinovi
Rossella
R
Bovino
Achiropita
A
Mattei
Silvia
S
Orlandini
Guido
G
Gatti
Rita
R
Savi
Mario
M
Sado
Yoshikazu
Y
Neri
Tauro M
TM
Allegri
Landino
L
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
D024141:Collagen Type IV; D012333:RNA, Messenger