The change of angiotensin II production and its receptor expression during wound healing: possible role of angiotensin II in wound healing / 中华整形外科杂志

<p><b>OBJECTIVE</b>This study was undertaken to observe the change in the local level of angiotensin II (Ang II) and the expression of its corresponding receptors AT1 and AT2 during wound healing, and explore the possible role of Ang II in wound healing .</p><p><b>METHODS</b>A model of full-thickness cutaneous wound was developed on the back of C57/BL6 mice. Specimens were taken from the wound of each mouse on the day 0, 1, 3, 5, 7, 9, 11, 13 and 15 after wounding. The change in the generation of Ang II in wounded tissue during the healing process was detected with ELISA. The proliferation and the apoptosis of cells were detected by bromodeoxyuridine (Brdu) and terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method in wounded skin during the healing process, respectively. The cellular localization and the mRNA level change of Ang II receptors in wounded tissue during healing were detected with immunostaining and RT-PCR.</p><p><b>RESULTS</b>Ang II produced in wounded skin was increased in the first 7 days to reach the peak, and then gradually decreased during wound healing. BrdU labeling index was increased gradually in the first 7 days to reach the peak, and then gradually decreased during wound healing. The number of TUNEL-positive cells was increased slowly in the first 7 days after wounding. The increase in the number of TUNEL-positive cells was more markedly after epithelization of the wound. In normal mice, AT1 and AT2 receptor were found positively expressed in the whole epidermal layer, while positive expression was only found in the endothelial cells of the capillary vessels within the dermal layer, and positive expression was also found in appendages of the skin, i. e. hair follicle, sweat gland and sebaceous gland respectively. Positive staining signal of both AT1 and AT2 receptors were increased in the first 7 days to reach the peak, then gradually decreased. Expression of AT2R was increased again following the epithelization of wound. The result of RT-PCR showed that the expression of both AT1 and AT2 receptors was detectable, and AT1 receptor was increased in the first 7 days to the peak, and then gradually decreased during wound healing, while AT2 receptor expression reached its peak value on day 7, then gradually decreased, and increased again following the epithelization of wound.</p><p><b>CONCLUSIONS</b>These results indicate that Ang II participate in wound repair and related to remolding in the late stage of wound healing through the change in production of angiotensin II and expression of AT1 and AT2 receptors. AT1 receptor might be closely associated with cell proliferation, while AT2 receptor might play a role in cell apoptosis and remolding during wound healing.</p>

The effect of angiotensin II on phosphoinositide-3 kinase/Akt cascade in cultured fibroblasts derived from patients with hypertrophic scars / 中华整形外科杂志

<p><b>OBJECTIVE</b>To study the effect of angiotensin II on phosphoinositide-3 kinase/Akt cascade in cultured fibroblasts derived from patients with hypertrophic scars.</p><p><b>METHODS</b>The expression of AT1 and AT2 receptor was detected by immunofluorescence staining. Cultured human skin fibroblasts were treated with Ang II (10(-9) - 10(-7) mol/L), with or without an AT1 receptor blocker, valsartan or an AT2 receptor antagonist, PD123319. The phosphorylation of Akt was detected by western blotting, and PI3K activity was measured by Assay of PI3-K activity.</p><p><b>RESULTS</b>Immunofluorescence staining showed that cultured fibroblasts derived from hypertrophic scars expressed both AT1 and AT2 receptors. Ang II increased Akt phosphorylation and PI3K activity in cultured hypertrophic scar fibroblasts in a dose- and time-dependent manner. Additionally, Ang II-induced Akt phosphorylation was blocked by wortmannin, a PI3-K inhibitor. This Ang II-activated PI3-K/Akt cascade was significantly inhibited by valsartan, an AT1 receptor specific blocker (P<0.05), whereas enhanced by PD123319, an AT2 receptor antagonist (P<0.05).</p><p><b>CONCLUSION</b>These results indicate that Ang II receptors regulates PI3-K/Akt cascade of hypertrophic scars fibroblasts via AT1 and AT2.</p>