Role And Mechanism Of RELM-β In Rat Hypoxia-induced Pulmonary Hypertension

Objective:We demonstrated the expression of Resistin-Like Molecule-β(RELM-β)within different time courses in chronic hypoxia induced pulmonary vascular remodeling. Moreover, by overexpressing and suppressing RELM-β in pulmonary of the rats, we investigated the role of RELM-β in hypoxic pulmonary hypertension.Methods : 1. We induced pulmonary vascular remodeling through chronic hypoxia exposure and detected the expression of RELM-β for different time courses(0 day, 3 days, 7 days, 14 days and 21 days) in lung tissue, bronchia alveolus lavage fluid(BALF) and blood serum. 2. Rats in chronic-hypoxia exposure had been given lentivirus intratracheally to knockdown RELM-β. Conversely, other rats had been given murine recombination RELM-β protein for overex-pression before normoxia exposure. 3. We evaluated the expression of RELM-β in lung tissue and pulmonary vascular remodeling throughout the pulmonary vascular bed of the rats. 4. We detected PI3K/Akt/m TOR, PKC/MAPKs expression in pulmonary artery walls.Results : 1. Chronic hypoxia induced pulmonary vessels significantly thickened and increased RELM-β in lung tissue, BALF and blood serum.2. Q-PCR and Western blot results reflected that hypoxia up-regulated RELM-β m RNA and protein ex-pression in lung tissue peaked at the 3rd day and then decreased steadily but were still above the baseline till the21 st day under hypoxia conditions. 3. The immunohistochemistry of lung sections demonstrated that hypoxia induced-RELM-β expressed in bronchial fibrous, alveolar epithelium and pul-monary vasculature. 4. The RELM-β protein was suppressed in rats with si RNA-lentivirus in hypoxia exposure, as well as pulmonary vascular remodeling. 5. Rats given murine recombination RELM-β protein to normoxia increased vessels thickened and the recruitment of inflammatory cells compared to controls.Conclusions:1. RELM-β was a secretory protein and could be secreted to lung tissue and blood. 2. RELM-β was expressed in bronchial epithelial and alveolar epithelium, and pulmonary vasculature to hypoxia.RELM-β up-regulated in a shot time and subsequently declined closing to the baseline. 3. Over-expression or suppression of RELM-β could enhance or decrease pulmonary vascular remodeling throughout PKC/MAPKs and PI3K/Akt/m TOR pathway.