Over-expression of thymosin 尾4 in granulomatous lung tissue with active pulmonary tuberculosis
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文摘
Recent studies have shown that thymosin 尾4 (T尾4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1伪 (HIF-1伪) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis.

We investigated the expression of T尾4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1伪 to compare their T尾4 expression patterns in patients' tissues and in the tissue microarray of TB patients.

T尾4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1伪 was similar to that of T尾4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with T尾4. However, the expression of T尾4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing T尾4.

We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of T尾4 was significantly higher in patients with pulmonary tuberculosis than in normal controls.

These data suggest that T尾4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1伪- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of T尾4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis.

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