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Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model
- Source :
- International journal of molecular medicine. 24(3)
- Publication Year :
- 2009
-
Abstract
- Fabry disease is a lysosomal storage disease caused by a deficiency of alpha-galactosidase A, which results in aberrant glycosphingolipid metabolism and accumulation of globotriaosylceramide (Gb3). Since a correlation between the level of Gb3 and clinical manifestations of Fabry disease has not been observed, we investigated potential diagnostic biomarkers. Hepatic and renal gene expression of male alpha-galactosidase A-deficient mice (Fabry mice) was compared with that of wild-type mice. Microarray analyses were performed using samples taken before and after intravenous infusion of alpha-galactosidase A. The identified genes were validated using quantitative real-time PCR and Western blot assay. Expression of hepatic Serum Amyloid A1 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8 and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide Y (Npy), Thrombospondin 2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels after enzyme replacement therapy, although the plasma concentrations of these proteins show heterogeneity. Upregulation of Saa1, S100a8, S100a9 and Lcn2 may modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and renal involvement in Fabry disease. Furthermore, these genes are promising targets for developing biomarkers for monitoring disease progression and therapeutic efficacy in patients with Fabry disease.
- Subjects :
- medicine.medical_specialty
Blotting, Western
Globotriaosylceramide
Biology
Lipocalin
Kidney
Thrombospondin 1
chemistry.chemical_compound
Mice
Lipocalin-2
Internal medicine
Genetics
Lysosomal storage disease
medicine
Animals
Neuropeptide Y
Oncogene Proteins
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Trihexosylceramides
Serum amyloid A1
Kidney metabolism
Reproducibility of Results
General Medicine
Enzyme replacement therapy
Genetic Therapy
medicine.disease
Fabry disease
Lipocalins
Blot
Disease Models, Animal
Endocrinology
chemistry
Gene Expression Regulation
Liver
alpha-Galactosidase
Fabry Disease
Acute-Phase Proteins
Subjects
Details
- ISSN :
- 11073756
- Volume :
- 24
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- International journal of molecular medicine
- Accession number :
- edsair.doi.dedup.....f30186f56a7bba00cd469be0c1ff86f9