PMID- 11841363
OWN - NLM
STAT- MEDLINE
DCOM- 20020314
LR  - 20190704
IS  - 0007-0963 (Print)
IS  - 0007-0963 (Linking)
VI  - 146
IP  - 1
DP  - 2002 Jan
TI  - Epidermal-dermal interactions regulate gelatinase activity in Apligraf, a 
      tissue-engineered human skin equivalent.
PG  - 26-31
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs 
      (TIMPs) have important functions during skin development, repair and maintenance. 
      MMP-2 and MMP-9 (gelatinase A and gelatinase B) are involved in regulating 
      keratinocyte migration. OBJECTIVES: To analyse whether Apligraf, a bilayered 
      tissue-engineered human skin equivalent (HSE), produces gelatinases and TIMPs and 
      whether or not epidermal-dermal interactions regulate MMP activity. METHODS: The 
      tissue distribution of MMP-2, MMP-9, TIMP-1, TIMP-2 and fibronectin was analysed 
      by immunohistochemistry. Secreted MMP activity was quantified by a fluorimetric 
      assay and gelatin zymography was used to monitor gelatinases in tissue culture 
      supernatants. RESULTS: Apligraf expressed MMP-2 and MMP-9 and contained 
      immunohistochemically detectable amounts of TIMP-1 and TIMP-2. The gelatinases 
      were predominantly produced in the epidermis, whereas immunostaining of TIMP-1 
      and TIMP-2 was largely confined to the dermal component of the HSE. Fibronectin 
      was expressed only in the dermis. Gelatin zymography demonstrated that intact 
      Apligraf produced both MMP-2 and MMP-9, the latter predominantly in its latent 
      form. Separation of the dermis from the epidermis resulted in an enhanced 
      production and activation of MMP-9 by the epidermal layer, and secretion of 
      latent and active MMP-2 by the dermal layer. Moreover, the incubation media of 
      the separated epidermis demonstrated significantly stronger MMP activity than did 
      intact Apligraf or its dermal component. CONCLUSIONS: These observations provide 
      evidence that epidermal-dermal interactions suppress epidermal gelatinase 
      activity. In addition, coexpression of TIMPs and fibronectin in the Apligraf 
      dermis suggests that the product has the potential to counteract the imbalance 
      between matrix production and degradation in chronic wounds and thus may support 
      wound re-epithelialization.
FAU - Osborne, C S
AU  - Osborne CS
AD  - TA Immunopathology/Dermatology, Novartis Pharma Research, 4002 Basel, 
      Switzerland.
FAU - Schmid, P
AU  - Schmid P
LA  - eng
PT  - Journal Article
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Apligraf)
RN  - 0 (Fibronectins)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Gelatinases)
SB  - IM
MH  - *Collagen
MH  - Dermis/*physiology
MH  - Epidermis/*physiology
MH  - Fibronectins/physiology
MH  - Fluorometry/methods
MH  - Gelatinases/*physiology
MH  - Humans
MH  - Tissue Inhibitor of Metalloproteinases/*physiology
MH  - Wound Healing/physiology
EDAT- 2002/02/14 10:00
MHDA- 2002/03/15 10:01
CRDT- 2002/02/14 10:00
PHST- 2002/02/14 10:00 [pubmed]
PHST- 2002/03/15 10:01 [medline]
PHST- 2002/02/14 10:00 [entrez]
AID - 4563 [pii]
AID - 10.1046/j.1365-2133.2002.04563.x [doi]
PST - ppublish
SO  - Br J Dermatol. 2002 Jan;146(1):26-31. doi: 10.1046/j.1365-2133.2002.04563.x.