Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells.

摘要: Accumulation of mesangial matrix is a pivotal event in the pathophysiology diabetic nephropathy. The molecular triggers for production are still being defined. Here, suppression subtractive hybridization identified 15 genes differentially induced when primary human cells exposed to high glucose (30 mM versus 5 mM) vitro. These included (a) known regulators cell activation nephropathy (fibronectin, caldesmon, thrombospondin, and plasminogen activator inhibitor-1), (b) novel genes, (c) whose induction by has not been reported. Prominent among latter were encoding cytoskeleton-associated proteins connective tissue growth factor (CTGF), modulator fibroblast production. In parallel experiments, elevated CTGF mRNA levels demonstrated glomeruli rats with streptozotocin-induced Mannitol provoked less expression vitro than glucose, excluding hyperosmolality as key stimulus. addition recombinant cultured enhanced extracellular proteins. High stimulated transforming beta1 (TGF-beta1), TGF-beta1 triggered expression. was partially suppressed anti-TGF-beta1 antibody protein kinase C inhibitor GF 109203X. Together, these data suggest that 1) stimulates TGFbeta1-dependent dependent pathways, 2) may be mediator TGFbeta1-driven within milieu.