Changes in global gene expression indicate disordered autophagy, apoptosis and inflammatory processes and downregulation of cytoskeletal signalling and neuronal development in patients with Niemann –Pick C disease

AbstractChanges in gene expression profiles were investigated in 23 patients with Niemann –Pick C1 disease (NPC). cDNA expression microarrays with subsequent validation by qRT-PCR were used. Comparison of NPC to control samples revealed upregulation of genes involved in inflammation (MMP3,THBS4), cytokine signalling (MMP3), extracellular matrix degradation (MMP3,CTSK), autophagy and apoptosis (CTSK,GPNMB,PTGIS), immune response (AKR1C3,RCAN2,PTGIS) and processes of neuronal development (RCAN2). Downregulated genes were associated with cytoskeletal signalling (ACTG2,CNN1); inflammation and oxidative stress (CNN1); inhibition of cell proliferation, migration and differentiation; ERK-MAPK pathway (COL4A1,COL4A2,CPA4); cell adhesion (IGFBP7); autophagy and apoptosis (CDH2,IGFBP7,COL4A2); neuronal function and development (CSRP1); and extracellular matrix stability (PLOD2). When comparing NPC and Gaucher patients together versus controls, upregulation ofSERPINB2 andIL13RA2 and downregulation ofCSRP1 andCNN1 were characteristic. Notably, in NPC patients, the expression ofPTGIS is upregulated while the expression ofPLOD2 is downregulated when compared to Gaucher patients or controls and potentially could serve to differentiate these patients. Interestingly, in NPC patients with (i) jaundice, splenomegaly and cognitive impairment/psychomotor delay —the expression ofACTG2 was especially downregulated; (ii) ataxia —the expression ofACTG2 andIGFBP5 was especially downregulated; an...

Source: Neurogenetics - January 10, 2020 Category: Genetics & Stem Cells Source Type: research