RESUMO
This paper explores the potential mechanism of microRNA-143–5p regulation effects on pulmonary arterysmooth muscle cells (PASMCs) functions in hypoxic pulmonary hypertension (HPH) via targeting HIF-1a,which may offer a new idea for HPH therapy. PASMCs were transfected with mimics control/miR-143–5pmimics or inhibitor control/miR-143–5p inhibitor. We used Western blotting and RT-qPCR to detect the proteinand mRNA expressions, CCK-8 assay to detect cellular viability, Annexin V-FITC/PI staining and caspase3/cleaved caspase-3 protein to evaluate cellular apoptosis, transwell migration experiment for cellularmigration measurement and Dual luciferase reporter gene assay to prove the target of miR-143–5p. Cells underhypoxic condition presented the decreased protein and mRNA expressions of a-smooth muscle actin (SM-aactin), Myocardin, smooth muscle myosin heavy chain (SMMHC), and smooth muscle-22a (SM22a),Calponin1 and Hypoxia-inducible factor-1a(HIF-1a), the increased cell viability and miR-143–5p level; Overexpression of miR-143–5p obviously reduced vascular smooth muscle-specific contraction marker proteinlevels and cellular apoptosis, increased cellular migration of PASMCs with hypoxia stimulation; Low-expression of miR-143–5p caused the opposite changes, while co-transfected with Si HIF-1a blocked thebeneficial effects of miR-143–5p inhibition on PASMCs under hypoxia. MicroRNA-143–5p can promote thephenotype conversion, proliferation and migration of pulmonary artery smooth muscle cells under hypoxiccondition through direct targeting of HIF-1a.
RESUMO
<p><b>OBJECTIVE</b>To establish the three-dimensional images of rat's alveolar bone and to evaluate the effects of nicotine on alveolar bone loss during the process of ligature-induced periodontitis with micro-computed tomography (micro-CT).</p><p><b>METHODS</b>Thirty-six adult male SD rats received silk ligatures around the cervix of the right second maxillary molars. Then the animals were randomly assigned to three groups and received daily intraperitoneal injections as follows: group A (control), saline solution; group B, nicotine, 0.83 mg x kg(-1) x d(-1); and group C, nicotine, 1.67 mg x kg(-1) x d(-1). Six animals in each group were randomly selected and sacrificed at day 14 and 28. Micro-CT examinations were used to evaluate the periodontal breakdown.</p><p><b>RESULTS</b>With the nicotine dose increased, bone mineral density (BMD), bone volume fraction (BVF), and trabecular thickness (TT) gradually reduced, while the trabecular spacing (TS) and alveolar bone loss (ABL) increased. At day 28, the ABL of group C (left, right) was (0.61 +/- 0.14) mm and (1.39 +/- 0.09) mm, and significantly higher than that of group B [(0.39 +/- 0.10) mm and (1.31 +/- 0.06) mm] and group A[(0.30 +/- 0.06) mm and (0.94 +/- 0.07) mm]. The BMD of group C, group B and group A at day 28 was [(617.86 +/- 34.27), (572.46 +/- 31.62) mg/cm3], [(660.04 +/- 36.73), (604.97 +/- 32.59) mg/cm3] and [(709.15 +/- 34.95), (657.04 +/- 30.06) mg/cm3] respectively.</p><p><b>CONCLUSIONS</b>Daily administration of nicotine results in significant bone loss and microstructure deteriorations in the trabeculae of alveolar bone.</p>