Differential expression of angiotensin receptors in human cutaneous wound healing.
BACKGROUND
Angiotensin AT1 and AT2 receptors are expressed in human skin. Furthermore, AT2 receptors have been reported to be upregulated during tissue repair and remodelling in various noncutaneous human tissues.


OBJECTIVE
Detection of alterations in angiotensin II receptor expression during wound healing in human skin.


METHODS
Three models were employed. (i) Primary human keratinocytes were razor scraped in culture flasks and alterations in the expression of angiotensin receptor mRNA determined by semiquantitative reverse transcription-polymerase chain reaction for 1-12 h thereafter. (ii) Early wound healing (48 h after cutting) was studied in punch biopsies from human skin ex vivo by means of immunohistochemical staining using polyclonal antibodies against the AT1 or AT2 receptor. (iii) In vivo wound healing was studied in sections of human cutaneous scars by immunohistochemistry to determine receptor expression early (2 days) and late (2 weeks-3 months) after surgery.


RESULTS
In all experimental settings, an upregulation of both receptor subtypes was noticed after wounding. Immunohistochemically stained skin sections showed a stronger expression of AT2 than of AT1 receptors within the area of scarring. Enhanced receptor expression was detectable as early as 24 h after injury and lasted for up to 3 months.


CONCLUSIONS
From these data, we conclude that angiotensin AT1 and AT2 receptors are upregulated in human cutaneous wounds, giving further support to the concept that angiotensin II plays a role even at an early stage during cutaneous wound healing.
Steckelings
U M
UM
Centre for Cardiovascular Research, Institute for Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, 10115 Berlin, Germany. ulrike.steckelings@charite.de
Henz
B M
BM
Wiehstutz
S
S
Unger
T
T
Artuc
M
M
D001706:Biopsy; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000293:injuries* / Q000378:metabolism; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin