PMID- 20846312
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20211020
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Print)
IS  - 0007-0963 (Linking)
VI  - 164
IP  - 1
DP  - 2011 Jan
TI  - Endoplasmic reticulum Ca2+ depletion activates XBP1 and controls terminal 
      differentiation in keratinocytes and epidermis.
PG  - 16-25
LID - 10.1111/j.1365-2133.2010.10046.x [doi]
AB  - BACKGROUND: Endoplasmic reticulum (ER) Ca(2+) depletion, previously shown to 
      signal pathological stress responses, has more recently been found also to 
      trigger homeostatic physiological processes such as differentiation. In 
      keratinocytes and epidermis, terminal differentiation and barrier repair require 
      physiological apoptosis and differentiation, as evidenced by protein synthesis, 
      caspase 14 expression, lipid secretion and stratum corneum (SC) formation. 
      OBJECTIVES: To investigate the role of Ca(2+) depletion-induced ER stress in 
      keratinocyte differentiation and barrier repair in vivo and in cell culture. 
      METHODS: The SERCA2 Ca(2+) pump inhibitor thapsigargin (TG) was used to deplete 
      ER calcium both in cultured keratinocytes and in mice. Levels of the ER stress 
      factor XBP1, loricrin, caspase 14, lipid synthesis and intracellular Ca(2+) were 
      compared after both TG treatment and barrier abrogation. RESULTS: We showed that 
      these components of terminal differentiation and barrier repair were signalled by 
      physiological ER stress, via release of stratum granulosum (SG) ER Ca(2+) stores. 
      We first found that keratinocyte and epidermal ER Ca(2+) depletion activated the 
      ER-stress-induced transcription factor XBP1. Next, we demonstrated that external 
      barrier perturbation resulted in both intracellular Ca(2+) emptying and XBP1 
      activation. Finally, we showed that TG treatment of intact skin did not perturb 
      the permeability barrier, yet stimulated and mimicked the physiological processes 
      of barrier recovery. CONCLUSIONS: This report is the first to quantify and 
      localize ER Ca(2+) loss after barrier perturbation and show that homeostatic 
      processes that restore barrier function in vivo can be reproduced solely by 
      releasing ER Ca(2+), via induction of physiological ER stress.
CI  - (c) 2010 No claim to original US government works. BJD (c) 2010 British Association 
      of Dermatologists 2010.
FAU - Celli, A
AU  - Celli A
AD  - Department of Dermatology, University of California, San Francisco, 4150 Clement 
      Street, San Francisco, CA 94121-1545, USA. celli.anna@gmail.com
FAU - Mackenzie, D S
AU  - Mackenzie DS
FAU - Crumrine, D S
AU  - Crumrine DS
FAU - Tu, C L
AU  - Tu CL
FAU - Hupe, M
AU  - Hupe M
FAU - Bikle, D D
AU  - Bikle DD
FAU - Elias, P M
AU  - Elias PM
FAU - Mauro, T M
AU  - Mauro TM
LA  - eng
GR  - R01 AR051930/AR/NIAMS NIH HHS/United States
GR  - R01 AR050023/AR/NIAMS NIH HHS/United States
GR  - R01 AR051930-04/AR/NIAMS NIH HHS/United States
GR  - R01 AR050023-07/AR/NIAMS NIH HHS/United States
GR  - R01 AR019098/AR/NIAMS NIH HHS/United States
GR  - AR19098/AR/NIAMS NIH HHS/United States
GR  - AR051930/AR/NIAMS NIH HHS/United States
GR  - R01 AG028492/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101129
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipids)
RN  - 0 (Membrane Proteins)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
RN  - 0 (Xbp1 protein, mouse)
RN  - 0 (loricrin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.4.22.- (Caspase 14)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Caspase 14/metabolism
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*metabolism
MH  - Endoplasmic Reticulum/drug effects/*metabolism/pathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermis/drug effects/*metabolism/pathology
MH  - Humans
MH  - Immunoblotting
MH  - Keratinocytes/*cytology/drug effects/pathology
MH  - Lipids/analysis
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Polymerase Chain Reaction
MH  - Regulatory Factor X Transcription Factors
MH  - Thapsigargin/pharmacology
MH  - Transcription Factors/*metabolism
MH  - X-Box Binding Protein 1
PMC - PMC3010253
MID - NIHMS238310
COIS- Conflict of interest: The authors do not have any conflict of interest
EDAT- 2010/09/18 06:00
MHDA- 2011/04/28 06:00
PMCR- 2012/01/01
CRDT- 2010/09/18 06:00
PHST- 2010/09/18 06:00 [entrez]
PHST- 2010/09/18 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - 10.1111/j.1365-2133.2010.10046.x [doi]
PST - ppublish
SO  - Br J Dermatol. 2011 Jan;164(1):16-25. doi: 10.1111/j.1365-2133.2010.10046.x. Epub 
      2010 Nov 29.