title: Cell Density-Dependent Upregulation of PDCD4 in Keratinocytes and Its Implications for Epidermal Homeostasis and Repair.
abstract: Programmed cell death 4 (PDCD4) is one multi-functional tumor suppressor inhibiting neoplastic transformation and tumor invasion. The role of PDCD4 in tumorigenesis has attracted more attention and has been systematically elucidated in cutaneous tumors. However, the normal biological function of PDCD4 in skin is still unclear. In this study, for the first time, we find that tumor suppressor PDCD4 is uniquely induced in a cell density-dependent manner in keratinocytes. To determine the potential role of PDCD4 in keratinocyte cell biology, we show that knockdown of PDCD4 by siRNAs can promote cell proliferation in lower cell density and partially impair contact inhibition in confluent HaCaT cells, indicating that PDCD4 serves as an important regulator of keratinocytes proliferation and contact inhibition in vitro. Further, knockdown of PDCD4 can induce upregulation of cyclin D1, one key regulator of the cell cycle. Furthermore, the expression patterns of PDCD4 in normal skin, different hair cycles and the process of wound healing are described in detail in vivo, which suggest a steady-state regulatory role of PDCD4 in epidermal homeostasis and wound healing. These findings provide a novel molecular mechanism for keratinocytes' biology and indicate that PDCD4 plays a role in epidermal homeostasis.
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. wangtmmu@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. ls13648315854@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Long
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. dunanadu@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. wangyusmmu@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. huiqinsun02@163.com.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute of Toxicology, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. zmzou@tmmu.edu.cn.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. wangjunping@tmmu.edu.cn.
authors.forename: Junping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. ranxinze@163.com.
authors.forename: Xinze
authors.initials: X
authors.lastname: Ran
authors.affiliation: Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, School of Preventive Medicine, Third Military Medical University, Chongqing 400038, China. suyp2003@163.com.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Su
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D051017:Apoptosis Regulatory Proteins; C498443:Pdcd4 protein, mouse; D016601:RNA-Binding Proteins; D019938:Cyclin D1
keywords: epidermal homeostasis; keratinocyte; programmed cell death 4 (PDCD4); proliferation; wound healing