Type VII collagen in Alport syndrome.
BACKGROUND
Absence or segmental distribution of the alpha5(IV) collagen chain along the epidermal basement membrane (EBM) is diagnostic of X-linked Alport syndrome (X-AS), but the typical morphologic alterations usually observed along the glomerular basement membrane (GBM) are lacking. However, several differences in protein composition exist between GBM and EBM, and such differences could account for a different phenotype with the same genetic defect. Type VII collagen is one of the major collagenous components of the EBM; the purpose of this study was to investigate the modifications of protein synthesis and expression of type VII collagen in the skin of patients with X-AS.


METHODS
The distribution of type VII collagen has been studied in 15 skin biopsies (10 from X-AS patients and 5 controls) by means of electron microscopy, immunofluorescence and confocal microscopy; type VII collagen mRNA expression was also measured by RT-PCR on the same skin fragments.


RESULTS
Protein and mRNA amounts for type VII collagen were significantly higher in skin samples from X-AS patients than in controls (P < 0.001); highest values were in cases in which alpha5(IV) was completely absent.


CONCLUSIONS
Our results indicate that lack of alpha5(IV) molecule significantly alters the assembly of extracellular matrix molecules other than alphax(IV) chains also at the EBM level. We suggest that the increased synthesis and deposition of type VII collagen is likely to balance the absence of stabilizing activity normally exerted by alpha5(IV).
Department of Experimental Medicine, La Sapienza University, Viale Regina Elena, 324, 00161 Rome Italy.
Konstantinos
K
Giannakakis
Laura
L
Massella
Daniele
D
Grassetti
Francesco
F
Dotta
Marie
M
Perez
Andrea Onetti
AO
Muda
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D024143:Collagen Type VII / Q000032:analysis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000378:metabolism*; D012867:Skin / Q000737:chemistry
D024143:Collagen Type VII