Erythroid differentiation regulator 1 (Erdr1) is a proapototic factor in human keratinocytes

Exp Dermatol. 2011 Nov;20(11):920-5. doi: 10.1111/j.1600-0625.2011.01354.x.

Abstract

Skin is constantly exposed to physical and chemical stressors. The exposure of keratinocytes to ultraviolet B (UVB) irradiation causes epidermal damage via induction of apoptosis. Erythroid differentiation regulator 1 (Erdr1) modulates growth and survival of cells under various stressful conditions, but the function of Erdr1 in human keratinocyte apoptosis has not been investigated so far. Here, we investigated the effect of Erdr1 on UVB-induced apoptosis in human keratinocytes and also examined the underlying regulatory mechanism. First, Erdr1 expression was detected in human primary keratinocytes and normal human skin tissues. Expression of Erdr1 was enhanced in human keratinocytes following UVB irradiation. Knock-down of Erdr1 led to resistance to UVB-induced apoptosis. Also, Erdr1 overexpression increased UVB-induced apoptosis and induced caspase-3 activation. Furthermore, the extracellular signal-regulated kinase (ERK) inhibitor PD98059 and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 significantly reduced Erdr1 expression following UVB irradiation. These results indicate that UVB induces Erdr1 via a MAPK-dependent mechanism. Taken together, these findings suggest that Erdr1 has a role as a proapoptotic factor in human keratinocytes and acts via ERK and p38 MAPK pathways. Therefore, Erdr1 may be a potential therapeutic target to reduce apoptosis in keratinocytes in conditions such as psoriasis and skin cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Apoptosis / radiation effects
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology*
  • Base Sequence
  • Caspase 3 / metabolism
  • Cell Line
  • Gene Knockdown Techniques
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / physiology*
  • Keratinocytes / radiation effects
  • MAP Kinase Signaling System
  • RNA, Small Interfering / genetics
  • Ultraviolet Rays / adverse effects

Substances

  • Apoptosis Regulatory Proteins
  • RNA, Small Interfering
  • CASP3 protein, human
  • Caspase 3