Retinoic acid signaling pathways in development and diseases

Abstract

Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging.

Left–right analysis of mammary gland development in retinoid X receptor-α +/− mice

“…RARs must heterodimerize with members of the RXR subfamily to regulate transcriptional activity of target genes, whereas RXRs can function in the absence of RARs, binding DNA as homodimers (reviewed by Das et al [35]). Thus, RXR receptors represent the common dimer partner for the family of retinoid receptors and play a critical central role in retinoid signalling.…”

The T-Box transcription factor 3 in development and cancer

“…All-trans RA, a metabolite of vitamin A (all-trans-retinol), plays an important role in embryo development, where it regulates gene transcription to modulate a number of biological processes, including cell proliferation, differentiation and apoptosis (88). Compromised RA signalling often occurs early in tumourigenesis, including in breast cancer (89).…”

Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

“…17 Retinoic acids play essential roles in biological processes including cell proliferation, differentiation, and apoptosis as well as development. 40 Moreover, they exhibit an antifibrotic action mediated through regulation of collagen turnover. 41,42 Corneal melting or scarring results from abnormal collagen remodeling in the corneal stroma.…”