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BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the right ventricular wall cardiomyocytes were also measured. Regulation of MTA1 on HIF-1α was determined in vitro. RESULTS MTA1 deficiency reduced the number of pulmonary alveolar capillaries compared to the wild-type mice. MTA1-KO mice exhibited a decreased expression of HIF-1α and VEGF in the lungs. The retarded growth of the MTA1-KO mice was also noticed during the first week after birth. Accordingly, MTA1 deficiency resulted in increased infant mortality. In surviving adult mice, MTA1 deficiency induced myocardial hypertrophy, highlighted by an increased heart weight/body weight ratio and larger cardiomyocytes. In cultured cells, HIF-1α and VEGF levels were significantly upregulated upon MTA1 overexpression, suggesting a close relationship between all 3 molecules. CONCLUSIONS MTA1 participates in the formation of pulmonary capillaries via stabilization of HIF-1α. This finding sheds new light on the function of MTA1 in lung development, opening new avenues for the diagnosis/treatment of related pulmonary diseases.

Comparing the lifespan and the proliferative potential of E. coli and MTB, we see a reverse relationship. E. coli live short, and grow fast. It just takes 18-20 minutes for them to duplicate. Conversely, MTBs live long, are quite tolerant to different environments, and grow so slowly that their duplication time exceeds 18 hrs. The duplication time of mycobacterium leprae is even longer, so that all the cultivation efforts have failed. Although nobody knows exactly how long these bacteria can live since they cannot be cultivated, it can be postulated that they live very long. That explains why leprosy is so difficult to cure.

Epithelial-mesenchymal transition (EMT) is the phenotypic transition of epithelial cells to mesenchymal cells characterized by loss of epithelial markers, loss of intercellular adherence and acquirement of mesenchymal cell markers and increased locomotive ability. EMT is widely considered to be a gene regulated process necessary for cancer metastasis. Yet it is a highly controversial issue. We here propose that EMT is an environmentally induced cell behavior. It is the mimicry of their living environment. It is a survival strategy, a way of immune escape. We also propose here that the epithelial cell markers may functionally act as tumor antigens since in the mesenchymal surroundings there are no other structures bearing the same antigens as epithelial cells.