Peroxisome proliferator–activated receptor γ (PPARγ) induces the gene expression of integrin αVβ5 to promote macrophage M2 polarization

Abstract

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 PPAR-responsive elements sites in the 5'-flanking regions of both murine and human integrin α_V and β₅ genes, respectively. In addition, we showed that PPARγ augmented the ligation of integrins α_V and β₅ Knockdown of integrin α_Vβ₅ by siRNA strategy or treatment with cilengitide, a potent inhibitor of integrin α_Vβ₅, attenuated PPARγ-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.