title: Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.
abstract: Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) 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 Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 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-1α was similar to that of Tβ4. 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 Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis.
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Jo
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea.
authors.forename: Mee Sun
authors.initials: MS
authors.lastname: Ock
authors.affiliation: Department of Biomedical Laboratory Science, Konyang University, Daejon, Republic of Korea.
authors.forename: Young-Bin
authors.initials: YB
authors.lastname: Yoo
authors.affiliation: Department of Pathology, Kosin University College of Medicine, Busan, Republic of Korea.
authors.forename: Bong-Kwon
authors.initials: BK
authors.lastname: Chun
authors.affiliation: Department of Internal Medicine, Kosin University College of Medicine, Busan, Republic of Korea. Electronic address: oaks70@daum.net.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Oak
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan, Republic of Korea; Institute for Medical Science, Kosin University College of Medicine, Busan, Republic of Korea. Electronic address: hcha@kosin.ac.kr.
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015769:Granuloma, Respiratory Tract / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013183:Sputum / Q000378:metabolism; D013947:Thymosin / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099201:Thymosin beta(4)
chemical_list: D015415:Biomarkers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D000099201:Thymosin beta(4)
keywords: HIF; Inflammation; Thymosin β4; Tuberculosis; VEGF