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Background and Purpose: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation.Experimental Approach: Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O2 on postnatal days 1-7) and the BPD model (100% O2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis.Key Results: Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets.Conclusion and Implications: These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD. [ABSTRACT FROM AUTHOR]

Aims The current study was carried out to evaluate the effect of advanced glycation end-products ( AGE) on cardiac aging and to explore its underlying mechanisms. Methods Neonatal rat cardiac fibroblasts were cultured and divided into four groups: control; AGE; AGE + receptor for AGE antibody and AGE + SB431542 (transforming growth factor-β [ TGF-β]/ Smad signaling pathway inhibitor, 10 μmol/L) group. After being cultured for 48 h, the cells were harvested and the senescence-associated beta-galactosidase expression was analyzed. Then the level of p16, TGF-β, Smad/p-smad and matrix metalloproteinases-2 was evaluated by western blot. Results Significantly increased senescence-associated beta-galactosidase activity as well as p16 level was observed in the AGE group. Furthermore, AGE also significantly increased the TGF-β1, p-smad2/3 and metalloproteinases-2 expression in cardiac fibroblasts (all P < 0.01). Meanwhile, either pretreatment with receptor for AGE-Ab or SB431542 significantly inhibited the upregulated cardiac senescence (beta-galactosidase activity and P16) and fibrosis-associated ( TGF-β1, p-smad2/3 and metalloproteinases-2) markers induced by AGE. Conclusions Taken together, all these results suggested that AGE are an important factor for cardiac aging and fibrosis, whereas the receptor for AGE and TGF-β/ Smad signaling pathway might be involved in the AGE-induced cardiac aging process. Geriatr Gerontol Int 2016; 16: 522-527. [ABSTRACT FROM AUTHOR]