The retinoid related orphan receptor RORα belongs to the steroid nuclear hormone receptor superfamily and functions as a transcription factor. RORα are critical in the regulation of many physiological processes and may have a role in several pathologies. It was reported that certain ligands can modulate RORα transcriptional activity.
The skin barrier is essential throughout life for animals to survive in an external environment. Although barely thicker than paper, the skin epidermis protects animals against major environmental stresses, such as water loss and microorganism infection. Previously, researchers have demonstrated that the nuclear hormone receptor RORα is expressed in epidermis/keratinocytes. RORα overexpression is enough to start the state of the cell differentiation process, whereas RORα shRNA gene silencing inhibits the expression of differentiation factors. The activation of RORα also regulates genes related to lipid metabolism, thereby has the potential to control the epidermal permeability barrier functions.
Transcription factors play an important role in control the fate of epidermal stem cell potential and differentiation, and therefore they are ideal drug targets for treating various skin diseases associated with barrier dysfunctions. This project will explore the potential of RORα agonist SR1078 in modulating keratinocyte differentiation in vitro and formation of epidermal barrier function in vivo. The results may provide new strategies for the treatment of skin diseases caused by barrier defects, such as atopic dermatitis. |