Emerging PPARγ-Independent Role of PPARγ Ligands in Lung Diseases

Figure 1

PPARγ ligands have multiple PPARγ-independent effects. In the classical PPARγ-dependent pathway, ligand-bound PPARγ forms a heterodimer with RXR and binds to PPARγ-response elements (PPREs) which leads to modulation of transcription. However, PPARγ ligands also exhibit direct effects that do not involve transcriptional activation by PPARγ/RXR. These direct effects may involve PPARγ protein interacting with PPARγ ligands in a “non-classical manner” (not involving RXR or PPRE) or may be completely independent of PPARγ (functioning even in the complete absence of PPARγ protein, i.e., direct effects). PPARγ-independent effects can alter multiple cellular programs including regulation of differentiation, inflammation, apoptosis and may be of significant therapeutic interest.