The cAMP response element modulator (CREM) in ulcerative colitis: Molecular mechanisms and therapeutic potential

Ulcerative colitis (UC) is one of the most important chronic inflammatory bowel diseases (IBD), and the aetiology of UC involves the interplay of genetic susceptibility, immune dysregulation, gut microbes and environmental factors. The cAMP response element modulator (CREM), a major effector of cAMP signalling, is a key transcription factor belonging to the cAMP response element binding protein (CREB) family. It integrates multiple upstream signaling pathways with distinct functions, such as cAMP/PKA, Ca²⁺/CaMKIV and AKT/mTOR. According to the urgent research, aberrant CREM expression occurs in colonic mucosal tissues and immune cells of UC patients which suggests its significant role in UC pathogenesis through multiple mechanisms. This review systemically summarizes the basic biological features of CREM, which comprises structural characteristics, isoform diversity, and regulatory networks in cellular signaling. In addition, we systematically analyse the main mechanisms by which CREM facilitates UC including the functions of immune cells, T cells, B cells and NK cells. Then we discuss the balance between pro-inflammatory and anti-inflammatory cytokines and the impact on intestinal barrier and gut microbiota. Ultimately, we will address the emerging resources, clinical potential of CREM as a healing target and pathway for future research. The purpose of this review is to provide novel insights into the pathogenesis of UC, which may contribute to optimizing clinical treatment and developing new therapeutic drugs.