Expression of hypoxia-inducible factor 1α, vascular endothelial growth factor and protein kinase B in lichen planus lesions

Abstract

Objective To explore relationships of expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and protein kinase B (P-Akt) with angiopoiesis and cell apoptosis. Methods Biopsy specimens were collected from skin lesions of 32 patients with lichen planus and normal skin of 20 patients with lipomyoma, and subjected to paraffin embedding. Immunohistochemical staining was performed to measure expression of HIF-1α, VEGF and P-Akt, and TUNEL technique was used to detect apoptosis of keratinocytes in these paraffin-embedded tissue sections. Microvessel density (MVD) was assessed by counting CD34-labeled vascular endothelial cells. Results HIF-1α, VEGF and P-Akt were moderately or strongly expressed in lichen planus lesions, but absent or weakly expressed in normal skin of controls, and the expression of HIF-1α, VEGF and P-Akt was significantly higher in the lichen planus group than in the control group (all P < 0.01). HIF-1α was mainly expressed in nuclei of keratinocytes, while VEGF and P-Akt were expressed in the cytoplasm of keratinocytes. In addition, the lichen planus group showed significantly increased MVD (21.27 ± 6.54 vs. 10.26 ± 1.10 microvessels/high-power (200 × ) field, t = 5.607, P < 0.01) and apoptosis rate of keratinocytes (72.81% ± 9.234% vs. 28.16% ± 3.464%, t = 8.431, P < 0.01) compared with the control group. Pearson correlation analysis showed that there were positive correlations between HIF-1α and VEGF expression, between VEGF and P-Akt expression, and between P-Akt and HIF-1α expression in the lichen planus group (r = 0.625, 0.453, 0.455, respectively, all P < 0.01), and expression of HIF-1α, VEGF and P-Akt was all positively correlated with MVD (r = 0.721, 0.646, 0.671, respectively, all P < 0.01). Conclusion HIF-1α and its downstream target genes VEGF and P-Akt may play a certain role in the occurrence of lichen planus. Key words: Lichen planus; Hypoxia-inducible factor 1, alpha subunit; Vascular endothelial growth factors; Protein kinases; Apoptosis