Expression of Constitutively Active cGMP-Dependent Protein Kinase Prevents Glucose Stimulation of Thrombospondin 1 Expression and TGF-β Activity

摘要: Hyperglycemia is a crucial factor in the development of diabetic nephropathy. We previously showed that high glucose upregulates thrombospondin 1 (TSP1)-dependent transforming growth (TGF)-β activation by altering cGMP-dependent protein kinase (PKG) activity as result decreased nitric oxide signaling. In present study, we concentrations significantly reduced endogenous PKG activity. To further examine mechanisms which regulates TSP1 expression and TSP1-dependent TGF-β activation, generated stably transfected rat mesangial cells (RMCs) with inducible tetracycline-induced gene catalytic domain PKG. After tetracycline induction, expressed cGMP-independent active kinase. Expression prevented glucose-mediated increases transcription no alteration mRNA stability. Glucose stimulation bioactivity were also downregulated. TGF-β-dependent fibronectin type IV collagen under conditions upon RMCs. These results show constitutively inhibits fibrogenic potential through repression bioactivity, suggesting transfer might provide new strategy for treatment renal fibrosis.