PMID- 19204729
OWN - NLM
STAT- MEDLINE
DCOM- 20090508
LR  - 20220331
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 458
IP  - 7237
DP  - 2009 Mar 26
TI  - Dynamic expression of epidermal caspase 8 simulates a wound healing response.
PG  - 519-23
LID - 10.1038/nature07687 [doi]
AB  - Tissue homeostasis and regeneration are regulated by an intricate balance of 
      seemingly competing processes-proliferation versus differentiation, and cell 
      death versus survival. Here we demonstrate that the loss of epidermal caspase 8, 
      an important mediator of apoptosis, recapitulates several phases of a wound 
      healing response in the mouse. The epidermal hyperplasia in the caspase 8 null 
      skin is the culmination of signals exchanged between epidermal keratinocytes, 
      dermal fibroblasts and leukocytic cells. This reciprocal interaction is initiated 
      by the paracrine signalling of interleukin 1alpha (IL1alpha), which activates 
      both skin stem cell proliferation and cutaneous inflammation. The non-canonical 
      secretion of IL1alpha is induced by a p38-MAPK-mediated upregulation of NALP3 
      (also known as NLRP3), leading to inflammasome assembly and caspase 1 activation. 
      Notably, the increased proliferation of basal keratinocytes is counterbalanced by 
      the growth arrest of suprabasal keratinocytes in the stratified epidermis by 
      IL1alpha-dependent NFkappaB signalling. Altogether, our findings illustrate how 
      the loss of caspase 8 can affect more than programmed cell death to alter the 
      local microenvironment and elicit processes common to wound repair and many 
      neoplastic skin disorders.
FAU - Lee, Pedro
AU  - Lee P
AD  - Section of Cell and Developmental Biology, Division of Biological Sciences, 
      Natural Science Building, Room 6311, 9500 Gilman Drive, MC 0380, La Jolla, 
      California 92093, USA.
FAU - Lee, Dai-Jen
AU  - Lee DJ
FAU - Chan, Carol
AU  - Chan C
FAU - Chen, Shih-Wei
AU  - Chen SW
FAU - Ch'en, Irene
AU  - Ch'en I
FAU - Jamora, Colin
AU  - Jamora C
LA  - eng
GR  - R01 AR053185-03/AR/NIAMS NIH HHS/United States
GR  - R01 AR053185-01A1/AR/NIAMS NIH HHS/United States
GR  - R01 AR053185/AR/NIAMS NIH HHS/United States
GR  - R01 AR053185-02/AR/NIAMS NIH HHS/United States
GR  - 5R01AR053185-03/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090208
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Carrier Proteins)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Alstrom Syndrome
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Caspase 1/metabolism
MH  - Caspase 8/biosynthesis/genetics/*metabolism
MH  - Cornea/cytology
MH  - Down-Regulation
MH  - Epidermal Cells
MH  - Epidermis/*enzymology/metabolism/pathology
MH  - Inflammation/pathology
MH  - Interleukin-1alpha/metabolism
MH  - Keratinocytes/cytology/metabolism
MH  - Mesoderm/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Paracrine Communication
MH  - Wound Healing/*physiology
PMC - PMC2666261
MID - NIHMS102693
EDAT- 2009/02/11 09:00
MHDA- 2009/05/09 09:00
PMCR- 2009/09/26
CRDT- 2009/02/11 09:00
PHST- 2008/08/13 00:00 [received]
PHST- 2008/12/09 00:00 [accepted]
PHST- 2009/02/11 09:00 [entrez]
PHST- 2009/02/11 09:00 [pubmed]
PHST- 2009/05/09 09:00 [medline]
PHST- 2009/09/26 00:00 [pmc-release]
AID - nature07687 [pii]
AID - 10.1038/nature07687 [doi]
PST - ppublish
SO  - Nature. 2009 Mar 26;458(7237):519-23. doi: 10.1038/nature07687. Epub 2009 Feb 8.