Related Experiment Video
Updated: Mar 28, 2026
Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
Cell Density-Dependent Upregulation of PDCD4 in Keratinocytes and Its Implications for Epidermal Homeostasis and
Tao Wang1, Shuang Long2, Na Zhao3
1Institute 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.
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.
Insights
Programmed cell death 4 (PDCD4) uniquely regulates keratinocyte proliferation and contact inhibition in skin. This tumor suppressor is vital for epidermal homeostasis and wound healing, revealing new insights into skin biology.
Area of Science:
- Cell Biology
- Dermatology
- Molecular Biology
Background:
- Programmed cell death 4 (PDCD4) is a known tumor suppressor involved in inhibiting neoplastic transformation and tumor invasion.
- While its role in cutaneous tumors is studied, its normal biological function in skin remains unclear.
Purpose of the Study:
- To investigate the normal biological function of PDCD4 in keratinocytes.
- To elucidate the role of PDCD4 in keratinocyte proliferation, contact inhibition, epidermal homeostasis, and wound healing.
Main Methods:
- Utilized siRNA to knock down PDCD4 expression in HaCaT keratinocytes.
- Analyzed cell proliferation, contact inhibition, and cyclin D1 expression.
- Examined PDCD4 expression patterns in normal skin, during hair cycles, and in wound healing models in vivo.
Main Results:
- PDCD4 is induced in keratinocytes in a cell density-dependent manner.
- PDCD4 knockdown promoted proliferation at lower densities and impaired contact inhibition in confluent cells.
- PDCD4 knockdown led to cyclin D1 upregulation, a key cell cycle regulator.
- In vivo, PDCD4 showed steady-state regulatory roles in epidermal homeostasis and wound healing.
Conclusions:
- PDCD4 acts as a crucial regulator of keratinocyte proliferation and contact inhibition in vitro.
- PDCD4 plays a significant role in maintaining epidermal homeostasis and facilitating wound healing in vivo.
- These findings reveal a novel molecular mechanism for keratinocyte biology and PDCD4's function in skin.
Related Concept Videos
01:12Renewal of Skin Epidermal Stem Cells
01:24Cells of the Epidermis
The cells in all these layers except the stratum basale are called keratinocytes, a type of cell that manufactures and stores the protein keratin. The keratinocytes in the stratum corneum are dead and regularly slough away, being replaced by cells from...