[The deletion of AT2 receptor gene antagonizes angiotensin II-induced apoptosis in fibroblasts].
OBJECTIVE
To study the expression of angiotensin II (Ang II) type 2 receptor (AT2) and its effect on the Ang II-induced apoptosis in fibroblasts.


METHODS
Skin fibroblasts were cultured from the embryos of the AT2 receptor gene deleted (AT2-/-) and wild-type (AT+/+) mice at 16 days of gestation. After Ang II being stimulated, the expressions of AT1 and AT2 receptor genes were examined by RT-PCR and the apoptotic changes were identified by genomic DNA electrophoresis, TUNEL staining and flow cytometry analysis of DNA contents. And they were compared in these two types of cultured fibroblasts.


RESULTS
Treated with Ang II for 48 h at the concentrations of 10(-8), 10(-7), 10(-6) and 10(-5) mol/L respectively, the expressions of AT1 and AT2 receptor genes were enhanced in a dose-dependent manner. Induced by Ang II for 72 h at the concentrations of 10(-6) and 10(-5) mol/L, genomic DNA fragmentation, one of convinced markers of cell apoptosis was found in the AT2+/+ fibroblasts, but not in the AT2-/- fibroblasts. The percentages of Ang-induced apoptosis of the AT2+/+ fibroblasts were (12.3 +/- 2.7)% (10(-6) mol/L) and (21.7 +/- 6.7)% (10(-5) mol/L) respectively.


CONCLUSIONS
The Ang II-induced apoptosis of fibroblasts was devoid after deletion of AT2 receptor gene.
Li
W
W
Division of Nephrology, General Hospital of Chinese PLA, Center of Nephrology, Beijing.
Chen
X
X
Ye
Y
Y
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D017353:Gene Deletion; D008297:Male; D051379:Mice; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics*; D012867:Skin / Q000166:cytology*
D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II