Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications

Figure 2

The activation of pathways triggered by hyperglycemia to induce TSP-1 expression. This diagram shows the pathways of PCK and Ang II induced by AGE; in addition, PKC also directly enhances Ang II activity. Then, two pathways induce some transcription factors binding the TSP-1 promoter to enhance the expression of TSP-1 via the MAPK pathway. ER stress and miRNAs also induce the expression of TSP-1 via activating NF-κB signaling. AGE: advanced glycation end products; DAG: diacylglycerol; PKC: protein kinase C; Ang II: angiotensin II; AT1: Ang II type 1; MAPK: mitogen-activated protein kinase; JNK: c-Jun amino terminal kinase; ER: endoplasmic reticulum; ERK: extracellular signal-regulated kinase; USF1/2: upstream stimulatory factors 1/2; Sp1: stimulating protein; NF-κB: nuclear factor-kappa B; Egr1: early growth response 1; AP1: activator protein 1.