ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of interferon regulatory factors (IRFs) on neointimal formation after vascular injury in the mouse, and its possible mechanism.</p><p><b>METHODS</b>Vascular injury was induced by polyethylene cuff placement around the left femoral artery of IRF-1-deficient mice and C57BL/6J mice. The mRNA expressions of IRF-1, IRF-2, angiotensin II type 2 (AT2) receptor, interleukin-1 beta converting enzyme (ICE), inducible nitric oxide synthase (iNOS) were detected by RT-PCR and immunohistochemical staining.</p><p><b>RESULTS</b>Neointimal formation after vascular injury was significantly greater in IRF-1-deficient mice than that in C57BL/6J mice (P<0.05). In contrast, TUNEL-positive nuclei to total nuclei in the neointima and media in vascular smooth muscle cell (VSMC) in the injured artery significantly attenuated in IRF-1-deficient mice compared to C57BL/6J mice (P<0.05). The expressions of AT2 receptor as well as pro-apoptotic genes such as ICE and iNOS in C57BL/6J mice were up-regulated in response to vascular injury, but this upregulation was attenuated in IRF-1-deficient mice.</p><p><b>CONCLUSIONS</b>Our results suggest that IRF-1 induces VSMC apoptosis and inhibits neointimal formation after vascular injury at least partly due to the upregulation of AT2 receptor, ICE and iNOS expressions. These results indicate that IRF-1 exerts an inhibitory effect on neointimal formation through the induction of apoptosis in VSMCs.</p>
Subject(s)
Animals , Male , Mice , Apoptosis , Physiology , Caspase 1 , Genetics , Metabolism , Femoral Artery , Pathology , Interferon Regulatory Factor-1 , Genetics , Metabolism , Interferon Regulatory Factor-2 , Genetics , Metabolism , Mice, Inbred C57BL , Mice, Knockout , Muscle, Smooth, Vascular , Cell Biology , Metabolism , Pathology , Nitric Oxide Synthase Type II , Genetics , Metabolism , Platelet Endothelial Cell Adhesion Molecule-1 , Genetics , Metabolism , Receptor, Angiotensin, Type 2 , Genetics , Metabolism , Tunica Intima , Pathology , PhysiologyABSTRACT
Prostate cancer ( PCa) is an important genitourinary malignancy with increasing morbidity and mortality. Glutathione S-transferase P1 ( GSTP1) , as a phrase- II enzyme, has an important role in the activation and detoxification of carcinogens. There is a close association between GSTP1 gene polymorphisms and the risk of Pca. GSTP1 CpG island hypermethylation can reliably distinguish Pca from benign prostatic hyperplasia( BPH) and promises to be an important molecular marker for the diagnosis of Pca. This paper summarizes the association of GSTP1 with the diagnosis and risk of Pca.