The development of efficient strategies for the improvement of wound repair requires understanding of the mechanisms underlying normal and impaired healing. Many factors can interfere with one or more phases of the cutaneous healing process, thus causing impaired wound healing in patients. Recent data implicates microRNAs as one such factor involved in wound repair. Because of the short sequence (~20 nt) and the tissue-specific activity, miRs may be targets for oligonucleotide (ON)-based RNA silencing therapy. This approach is particularly promising in the skin due to the accessibility of this tissue that allows local miR manipulation. miR-29 regulates collagen production by synovial fibroblasts and is a new therapeutic target in the Phase I clinical trial for cutaneous sclerosis. However, the regulation and functions of miR-29 in homeostatic and regenerating epidermis remain largely unknown. Our previous work identified an important function of miR-29s in regulating desmosomes in normal and hyperproliferative epidermis. In this project, we will use modified antisense miR-29 ON for efficient delivery, tracking, and downregulation of miR-29 function in vivo. Using miR crosslinking and immunoprecipitation (miR-CLIP) approach, we will identify new miR-29 targets regulating growth and differentiation of human keratinocytes.
The project in our group has three following objectives:
Objective 1. Uncover new RNA targets of miR-29s in human keratinocytes by miR-CLIP.
Objective 2. Determine the effect of miR-29 inhibition on wound healing in mice in vivo.
Objective 3. Determine the effect of miR-29 inhibition on human epidermal repair ex vivo.