Peroxisome proliferator-activated receptor γ (PPARγ) induces the gene expression of integrin α_vβ₅ to promote macrophage M2 polarization

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily and polarizes the macrophages into an anti-inflammatory M2 state. Integrins are transmembrane receptors that drive various cellular functions, including monocyte adhesion and foam cell formation. In this study, we first reported that the expression of integrins α_v and β₅ was up-regulated by PPARγ activation in RAW264.7 cells and human peripheral blood monocytes. Luciferase reporter and ChIP assay revealed that PPARγ directly bound to the potential PPARresponsive elements sites in the 5'-flanking regions of both murine and human integrinα_v andβ₅ genes, respectively. In addition, we showed thatPPARγ augmented the ligation of integrinsα_v andβ₅. Knockdown of integrinα_vβ₅ by siRNA strategy or treatment with cilengitide, a potent inhibitor of integrinα_vβ₅, attenuatedPPARγ-induced expression of Ym1 (chitinase-like protein 3), Arg1 (Arginase1), Fizz1 (resistin-like molecule RELMα), and other M2 marker genes, suggesting that the heterodimers of integrin α_vβ₅ were involved in PPARγ-induced M2 polarization. In conclusion, these results provided novel evidence that PPARγ-mediated gene expression and the ensuing ligation of integrins α_v and β₅ are implicated in macrophage M2 polarization.