Type VII collagen in Alport syndrome

Konstantinos Giannakakis, Laura Massella, Daniele Grassetti, Francesco Dotta, Marie Perez, Andrea Onetti Muda

Research output: Contribution to journalArticle

Abstract

Background. Absence or segmental distribution of the α5(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 α5(IV) was completely absent. Conclusions. Our results indicate that lack of α5(IV) molecule significantly alters the assembly of extracellular matrix molecules other than αx(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 α5(IV).

Original languageEnglish
Pages (from-to)3501-3507
Number of pages7
JournalNephrology Dialysis Transplantation
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Alport syndrome
  • Confocal microscopy
  • Dermoepidermal junction
  • RNA analysis
  • Type VII collagen

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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    Giannakakis, K., Massella, L., Grassetti, D., Dotta, F., Perez, M., & Muda, A. O. (2007). Type VII collagen in Alport syndrome. Nephrology Dialysis Transplantation, 22(12), 3501-3507. https://doi.org/10.1093/ndt/gfm481