Cutaneous wound healing is a complicated process involving inflammation,cell migration,proliferation,and tissue remolding.Its known to all that both wounds and cancer tissue have highlighted remarkable similarities with common cellular and molecular mechanisims.Upon skin injury,wound activates cancer-provoking genes and the repair cells exhibits a similar behavior like cancer cells,which are critical for normal wound healing.However,in contrast to cancer tissue,the process of wound healing is self-limiting,resulting in controlled cell proliferation,differentiation,migration and remodeling.Logically,the self-limiting of wound healing is partly due to the function of tumor suppressor genes.While the role of tumor suppressors in epidermal homeostasis and repair is still unclear.Here we show that the new tumor suppressor programmed cell death 4 (PDCD4) is induced in a cell density-dependent manner in HaCaT keratinocyte cells and this upregulation of PDCD4 protein is in accord with induced mRNA level.To determine the potential role of PDCD4 in keratinocyte cell biology,we show that knockdown of PDCD4 by two siRNAs can promote cell proliferation in lower cell density and partially impair contact inhibition in confluent HaCaT cells.In normal mouse skin tissue,PDCD4 is expressed mainly in hair follicle,sweat gland and interfollicular epidermis and displays diffuse cytoplasmic staining.Meanwhile,we find that there is significantly enhanced expression of PDCD4 in anagen hair follicle than that in telogen hair follicle and there is mutual inverse expression of PDCD4 and Ki67 in the anagen hair follicle.Then,the expression pattern of PDCD4 in repaired epidermis is examined using excision wound model.We frnd that PDCD4 is reduced in the activated migratory keratinocytes during reepithelialization.While,enhanced nucleus-staining PDCD4 is detected in the hyperproliferative wound epidermis as early as 7-day wound.Both the enhanced nucleus and cytoplasm staining of PDCD4 are observed in the epidermal maturation stage of reepithelialization in 16-day and 25-day wounds.Thus,our results suggest that tumor suppressor PDCD4 is uniquely induced in a cell density-dependent manner in keratinocyte cells and serves as important regulator of keratinocyte cell proliferation and contact inhibition in vitro.And whats more,enhanced expression of PDCD4 is detected in both anagen hair follicle and transient hyperproliferative wound epidermis in vivo,which suggests the important steady-state regulating role of PDCD4 in epidermal homeostasis and wound healing.