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IL-13 Enhances Mecenchymal Transition of Pulmonary Artery Endothelial Cells Through Down-Regulation of miR-424 and miR-503 In Vitro
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A2100 - IL-13 Enhances Mecenchymal Transition of Pulmonary Artery Endothelial Cells Through Down-Regulation of miR-424 and miR-503 In Vitro
Author Block: K. Takagi1, M. Yamakuchi2, T. Matsuyama2, S. Misono2, K. Machida2, T. Hashiguchi2, H. Inoue2; 1Kagoshima university graduate school of medical and dental sciences, Kagoshima City, Japan, 2Kagoshima university graduate school of medical and dental sciences, Kagoshima city, Japan.
RATIONALE: Pulmonary arterial hypertension (PAH) has a major effect on quality of life and life expectancy with function degeneracy of lungs and right heart. PAH is characterized by progressive vascular changes leading to the obliteration of pulmonary arteries. IL-13, one of the type 2 cytokines mainly associated with allergic diseases, has been recently reported to be associated with PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored. We examined how IL-13 changes phenotype of pulmonary artery endothelial cells in vitro. METHODS: Using primary human pulmonary artery endothelial cells (HPAECs), we examined the effects of recombinant human IL-13. Expression levels of mRNA and protein were analyzed by qRT-PCR and Western blotting. miRNA expression levels were determined by qPCR. The functional studies of HPAECs were performed using short interfering RNAs (siRNA), and Precursor or Antisense oligonucletides of certain miRNAs. Cellular proliferation and migration were accessed by XTT assay and scratch assay, respectively. RESULTS: IL-13 increased expressions of Rictor, which is a key molecule of mammalian target of rapamycin complex 2, and mecenchymal markers in HPAECs. IL-13 induced HPAECs migration via Rictor. Rictor was directly regulated by both miR-424 and miR-503. We confirmed that IL-13 inhibited the expression of miR-424 and miR-503 and overexpression of miR-424 and miR-503 restored IL-13 induced HPAECs migration through the reduction of Rictor. The pathway from IL-13 to miR-424 and miR-503 was present through phosphorylation of STAT6 and inhibiting phosphorylation of HDAC class 2a. CONCLUSIONS: These findings indicate that IL-13 enhanced mecenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424 and miR-503, and suggest that IL-13 takes some roles in exacerbating PAH.
Author Block: K. Takagi1, M. Yamakuchi2, T. Matsuyama2, S. Misono2, K. Machida2, T. Hashiguchi2, H. Inoue2; 1Kagoshima university graduate school of medical and dental sciences, Kagoshima City, Japan, 2Kagoshima university graduate school of medical and dental sciences, Kagoshima city, Japan.
RATIONALE: Pulmonary arterial hypertension (PAH) has a major effect on quality of life and life expectancy with function degeneracy of lungs and right heart. PAH is characterized by progressive vascular changes leading to the obliteration of pulmonary arteries. IL-13, one of the type 2 cytokines mainly associated with allergic diseases, has been recently reported to be associated with PAH. But a direct pathological role of IL-13 in the development of PAH has not been explored. We examined how IL-13 changes phenotype of pulmonary artery endothelial cells in vitro. METHODS: Using primary human pulmonary artery endothelial cells (HPAECs), we examined the effects of recombinant human IL-13. Expression levels of mRNA and protein were analyzed by qRT-PCR and Western blotting. miRNA expression levels were determined by qPCR. The functional studies of HPAECs were performed using short interfering RNAs (siRNA), and Precursor or Antisense oligonucletides of certain miRNAs. Cellular proliferation and migration were accessed by XTT assay and scratch assay, respectively. RESULTS: IL-13 increased expressions of Rictor, which is a key molecule of mammalian target of rapamycin complex 2, and mecenchymal markers in HPAECs. IL-13 induced HPAECs migration via Rictor. Rictor was directly regulated by both miR-424 and miR-503. We confirmed that IL-13 inhibited the expression of miR-424 and miR-503 and overexpression of miR-424 and miR-503 restored IL-13 induced HPAECs migration through the reduction of Rictor. The pathway from IL-13 to miR-424 and miR-503 was present through phosphorylation of STAT6 and inhibiting phosphorylation of HDAC class 2a. CONCLUSIONS: These findings indicate that IL-13 enhanced mecenchymal transition of pulmonary artery endothelial cells via down-regulation of miR-424 and miR-503, and suggest that IL-13 takes some roles in exacerbating PAH.
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