This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Dr. Wan is presently an assistant professor at Providence College, which is only 2 miles from our institution.Water channel aquaporins (AQPs) are a family of small, hydrophobic, integral membrane proteins that are expressed widely in animal and plant kingdoms, with 13 members having thus far been identified in mammals. Aquaporin-3 (AQP3), functionally expressing in human skin keratinocytes and fibroblasts, facilitates water and glycerol movement into and out of the skin and plays an important role in skin physiology and pathology. However, the possible role of AQPs in human epidermal stem cells has not been fully explored.Stem cells are characterized by their prolonged self-renewal capacity and by their asymmetric replication. Asymmetric replication is a special property of stem cells: with every cell division, one of the cells retains its self-renewing capacity, whereas the other enters a differentiation pathway and joins a mature non-dividing population. Epidermis of the skin contains a subpopulation of basal cells called epidermal stem cells that exhibit the properties expected of somatic stem cells.Epidermal stem cells are multipotent in that they can reconstitute all the components of the cutaneous epithelium: epidermis, hair follicles and sebaceous glands. They are easily accessible and hold great promise for therapeutic applications in skin homeostasis and wound repair as well as skin cancer. A large number of factors have been implicated in skin morphogenesis and the determination of epidermal stem cell fate. Besides the Wnt/Lef/Tcf pathway and c-myc, two play critical roles in epidermal stem cell lineage determination and proliferation, they include p63, hairless and members of the Shh, Notch and TGF-beta-signalling pathways. However the possible role of AQPs in epidermal stem cell biology or physiology is not fully studied.
The specific aims are: 1. To test the expression of AQP1, AQP3 or AQP4 in human epidermal stem cells; 2. To test the possible involvement of AQPs in human epidermal stem cells migration; 3. To test the possible role of AQPs in human epidermal stem cell renewal or proliferation potential; 4. To test the role of AQPs in epidermal stem cells differentiation.
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