Triterpenoids, Vitamin D, and TGF-β/Smad Signaling in Inflammation and Cancer

Abstract

The transforming growth factor-B (TGF-~) superfamily interacts with the nuclear receptor superfamily in a variety of cell types. The vitamin D receptor (VDR) and the peroxisome proliferator activated receptor-y (PPAR-y) are among the members of the nuclear receptor superfamily that after activation by their ligands interact with the TGF-~/Smad system to modulate cellular responses. This chapter discusses the importance of interactions between nuclear receptors and the TGF-~/ Smad system in inflammation as well as in cancer. Crosstalk between the TGF-~/Smad system and nuclear receptors occurs at multiple levels and will be discussed later in this chapter when describing the role of nuclear receptors and their ligands such as vitamin D derivatives and triterpenoids on (a) modulation of TGF-~/Smadsignaling, (b) interactions of nuclear receptors with Smads, and (c) the consequences of their interactions in diseases such as inflammation and cancer. Understanding crosstalk between the TGF-~/Smad system and the nuclear receptor superfamily may give new insights for the possible use of nuclear receptor ligands for the treatment and prevention of these and other diseases.