SUMOylation Of PPARγ1 Inhibit Macrophage M2 Polarization Induced By IL-4

Macrophage can polarize to dinstinct functional phenotypes which play an important role in many pathological and physiological process through specific transcription factors,depending on different stimulation.The peroxisome proliferator activated receptor gamma(PPARγ)are a subset of the nuclear receptor superfamily of ligand-inducible transcription factors,which controls the expression of networks of genes involved in adipogenesis,adipocyte differentiation,lipid metabolism,glucose homeostasis as well as macrophage development and regulates its functions.It has been reported that as a transcription factor the transcription ability of PPAR is regulated by its expression,endogenous ligand and also by post-translational modifications including SUMOylation.Recent reports indicated that IL-4 can induce PPARγ and natural ligand production which promote the expression of target genes,during the program of macrophage polarize to “M2” macrophage stimulated by IL-4.Although the expression,target gene and its biofunctions have been reported before,the existence and function of the SUMOylation of PPARγ1(an important post-translational modification of PPARγ)have not been reported yet.In this study,we found that the endogenous SUMOylation of PPARγ1 is decreased in the model of macrophage polarize to alternative activity macrophage when treated by IL-4,and identified PPARγ1 is sumoylated at Lys77,which can be desumoylated by SENP1.SUMOylation deficiency K77 R made PPARγ easily bind to the regulation element of Arg1,showing more transcription activity.Now,It can be concluded that the SUMOylation of PPARγ at K77 whose function is to inhibit transactivation decreased,promoting PPARγ binds to the pomoter of its target gene,promoting macrophage M2 polarization under IL-4 treatment.