The Role of PPAR Gamma in Systemic Sclerosis

Figure 2

Smad and non-Smad signaling TGF-β pathways and potential effects of PPARγ ligands. Binding of TGF-β to type 2 TGF-β receptor (TGF-βRII) recruits type 1 TGF-β receptors (TGF-βRI), forming a heterotetrameric structure that phosphorylates Smad2 and Smad3, which then binds to Smad4. Smad complex then translocates to the nucleus, where it interacts with various transcription factors to regulate the transcription of target genes (COL1A1, COL1A2, ASMA, CTGF). After TGF-β binding, TGF-βRII recruits a TGF-βRI and activates it by phosphorylation. Nonclassic pathways are also illustrated. PPARγ ligands can block TGF-β signaling by blocking Smad and non-Smad pathways.