Role of angiotensin II receptor subtypes in conjunctival wound healing.
OBJECTIVE
To investigate the role of angiotensin II (Ang II) receptor subtypes in subconjunctival injury.


METHODS
A wound-healing model was developed by subconjunctival blunt dissection in male wild-type, AT1a receptor-deficient (AT1aKO) and AT2 receptor-deficient (AT2KO) mice. Collagen deposition and cell infiltration were evaluated histologically. Expression of collagen, matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by real-time PCR.


RESULTS
Subconjunctival injury increased the infiltration of inflammatory cells, collagen deposition in the subconjunctival space, and the expression of collagen type I and type III, TIMP-1 and MMP2. In AT1aKO mice, collagen deposition, cell infiltration, and expression of collagen and TIMP-1 were inhibited, but MMP2 expression was enhanced. In contrast, in AT2KO mice, the increase in collagen deposition, cell infiltration, and expression of collagen and TIMP-1 were further enhanced.


CONCLUSIONS
These results indicate that AT1a and AT2 receptor stimulation may in addition to other mechanisms be antagonistically involved in the wound-healing process after subconjunctival injury.
Mizoue
Shiro
S
Department of Ophthalmology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Ehime, Japan.
Iwai
Masaru
M
Ide
Ayumi
A
Suzuki
Jun
J
Horiuchi
Masatsugu
M
Shiraishi
Atsushi
A
Ohashi
Yuichi
Y
D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003228:Conjunctiva / Q000293:injuries* / Q000378:metabolism; D004195:Disease Models, Animal; D015807:Eye Injuries, Penetrating / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020778:Matrix Metalloproteinase 2