Fibroblast expression of collagens and proteoglycans is altered in aspartylglucosaminuria, a lysosomal storage disease

Biochim Biophys Acta. 1994 Feb 22;1225(3):264-70. doi: 10.1016/0925-4439(94)90005-1.


Aspartylglucosaminuria (AGU), a lysosomal storage disease caused by deficient activity of aspartylglucosaminidase (E.C., is characterised by progressive mental retardation and variable connective tissue signs. The ultrastructure of collagen fibrils in skin of AGU patients is abnormal and their fibroblasts synthesise reduced amounts of collagens [Näntö-Salonen et al. (1984) Lab invest. 51: 464-468]. In this work we measured the steady-state messenger RNA levels of several extracellular matrix components in skin fibroblast cultures of two patients homozygous for the most prevalent mutation (AGUFin) causing the disease in Finland. In confluent cultures the steady-state mRNA concentrations of type I and III collagens were reduced to 0.5-20% of control values. Almost as marked reduction was observed in the mRNA level of biglycan, a small interstitial proteoglycan whereas that of decorin, a closely related, collagen fibril-associated proteoglycan, was increased several-fold. Elevated decorin and decreased biglycan mRNA levels reflected the amounts of the produced corresponding proteoglycans. The differences in the mRNA levels become more pronounced with the time the cells were in culture. Fibronectin mRNA concentrations were similar in AGU and control fibroblasts. Changes in the expression and synthesis of extracellular matrix components might be related to the connective tissue symptoms of the patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analogs & derivatives*
  • Acetylglucosamine / genetics
  • Acetylglucosamine / urine
  • Aspartylglucosaminuria
  • Cells, Cultured
  • Collagen / metabolism*
  • Extracellular Matrix / metabolism
  • Fibroblasts / metabolism
  • Humans
  • Lysosomal Storage Diseases / metabolism*
  • Procollagen / genetics
  • Proteoglycans / metabolism*
  • RNA, Messenger / analysis
  • RNA, Messenger / isolation & purification
  • Skin / metabolism*
  • Sulfur Radioisotopes


  • Procollagen
  • Proteoglycans
  • RNA, Messenger
  • Sulfur Radioisotopes
  • N-acetylglucosaminylasparagine
  • Collagen
  • Acetylglucosamine