Peroxisome proliferator-activated receptor (PPARγ) induces the gene expression of integrin V5 to promote macrophage M2 polarization

Peroxisome proliferator-activated receptor (PPAR) 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 (V) and (5) was up-regulated by PPAR activation in RAW264.7 cells and human peripheral blood monocytes. Luciferase reporter and ChIP assay revealed that PPAR directly bound to the potential PPAR-responsive elements sites in the 5-flanking regions of both murine and human integrin (V) and (5) genes, respectively. In addition, we showed that PPAR augmented the ligation of integrins (V) and (5). Knockdown of integrin (V5) by siRNA strategy or treatment with cilengitide, a potent inhibitor of integrin (V5), attenuated PPAR-induced expression of Ym1 (chitinase-like protein 3), Arg1 (Arginase1), Fizz1 (resistin-like molecule RELM), and other M2 marker genes, suggesting that the heterodimers of integrin (V5) were involved in PPAR-induced M2 polarization. In conclusion, these results provided novel evidence that PPAR-mediated gene expression and the ensuing ligation of integrins (V) and (5) are implicated in macrophage M2 polarization.