PMID- 15246741
OWN - NLM
STAT- MEDLINE
DCOM- 20050302
LR  - 20191210
IS  - 0047-6374 (Print)
IS  - 0047-6374 (Linking)
VI  - 125
IP  - 7
DP  - 2004 Jul
TI  - Retinoic acid receptor alpha expression and cutaneous ageing.
PG  - 465-73
AB  - Intrinsic ageing of human skin is a subtle and gradual process that demonstrates 
      few clinical or histological features until old age (>70 years). Initial work 
      indicates that aged skin is "retinoid sensitive" but there is little data on the 
      role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin 
      ageing. As nuclear retinoid receptors have been implicated in ageing in rodents, 
      we studied the distribution of these receptors in intrinsically aged as compared 
      to young, photoprotected human skin. We found that intrinsic ageing of skin in 
      vivo is accompanied by significant increases of RAR alpha mRNA and protein 
      whereas other isoforms show no alteration with age. In vitro transfection of 
      COS-1 cells with the RAR alpha gene induces expression of matrix 
      metalloproteinase-1 (MMP-1), an enzyme known to play an active role in 
      remodelling of the dermis in intrinsically aged and photoaged skin. Furthermore, 
      addition of all-trans retinoic acid (RA) to cultures of RAR alpha-transfected 
      COS-1 cells diminishes RAR alpha and returns levels of MMP-1 to those approaching 
      baseline. These results demonstrate that intrinsic ageing of human skin is 
      accompanied by significant elevation in the content of RAR alpha and that 
      over-expression of RAR alpha influences expression of MMP-1, an important 
      mediator of skin ageing.
FAU - Watson, Rachel E B
AU  - Watson RE
AD  - Dermatopharmacology Unit, Dermatology Centre, University of Manchester, Irving 
      Building, Hope Hospital, Salford, Manchester M6 8HD, UK.
FAU - Arjuna Ratnayaka, J
AU  - Arjuna Ratnayaka J
FAU - Brooke, Rebecca C C
AU  - Brooke RC
FAU - Yee-Sit-Yu, Sharon
AU  - Yee-Sit-Yu S
FAU - Ancian, Philippe
AU  - Ancian P
FAU - Griffiths, Christopher E M
AU  - Griffiths CE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Mech Ageing Dev
JT  - Mechanisms of ageing and development
JID - 0347227
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - COS Cells/drug effects
MH  - Cellular Senescence/physiology
MH  - Chlorocebus aethiops
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - HSP70 Heat-Shock Proteins/genetics/metabolism
MH  - Humans
MH  - Male
MH  - Matrix Metalloproteinase 1/drug effects/genetics/metabolism
MH  - Receptors, Retinoic Acid/drug effects/genetics/*metabolism
MH  - Retinoic Acid Receptor alpha
MH  - Skin Aging/*physiology
MH  - Tretinoin/pharmacology
EDAT- 2004/07/13 05:00
MHDA- 2005/03/03 09:00
CRDT- 2004/07/13 05:00
PHST- 2004/01/08 00:00 [received]
PHST- 2004/03/19 00:00 [revised]
PHST- 2004/03/22 00:00 [accepted]
PHST- 2004/07/13 05:00 [pubmed]
PHST- 2005/03/03 09:00 [medline]
PHST- 2004/07/13 05:00 [entrez]
AID - S0047637404000880 [pii]
AID - 10.1016/j.mad.2004.03.008 [doi]
PST - ppublish
SO  - Mech Ageing Dev. 2004 Jul;125(7):465-73. doi: 10.1016/j.mad.2004.03.008.