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Báo cáo y học: " Krüppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: " Krüppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension. | Courboulin et al. Respiratory Research 2011 12 128 http respiratory-research.eom content 12 1 128 RESPIRATORY RESEARCH RESEARCH Open Access Kruppel-like Factor 5 contributes to pulmonary artery smooth muscle proliferation and resistance to apoptosis in human pulmonary arterial hypertension Audrey Courboulin Véronique L Tremblay Marjorie Barrier Jolyane Meloche Maria Helena Jacob Mathilde Chapolard Malik Bisserier Roxane Paulin Caroline Lambert Steeve Provencher and Sébastien Bonnet Background Pulmonary arterial hypertension PAH is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell PASMC and suppressed apoptosis. This phenotype has been associated with the upregulation of the oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization decreasing apoptosis and the upregulation of growth factor and cytokines like PDGF IL-6 and vasoactive agent like endothelin-1 ET-1 promoting PASMC proliferation. Kruppel-like factor 5 KLF5 is a zinc-finger-type transcription factor implicated in the regulation of cell differentiation proliferation migration and apoptosis. Recent studies have demonstrated the implication of KLF5 in tissue remodeling in cardiovascular diseases such as atherosclerosis restenosis and cardiac hypertrophy. Nonetheless the implication of KLF5 in pulmonary arterial hypertension PAH remains unknown. We hypothesized that KLF5 up-regulation in PAH triggers PASMC proliferation and resistance to apoptosis. Methods and results We showed that KFL5 is upregulated in both human lung biopsies and cultured human PASMC isolated from distal pulmonary arteries from PAH patients compared to controls. Using stimulation experiments we demonstrated that PDGF ET-1 and IL-6 trigger KLF-5 activation in control PASMC to a level similar to the one seen in PAH-PASMC. Inhibition of the STAT3 pathway abrogates KLF5 activation in PAH-PASMC. Once activated KLF5 promotes cyclin B1 upregulation and promotes .