LncRNA NEAT1 regulates pulmonary fibrosis through miR-9-5p and TGF-ß signaling pathway.

OBJECTIVE: Pulmonary fibrosis (PF) is a chronic lung disease with complex pathogenesis and poor prognosis. Studies had demonstrated that long non-coding RNAs (lncRNAs) play an important role in the development of fibrosis. We explored the roles of NEAT1 in PF progression in this study. PATIENTS AND METHODS: PF tissues and TGF-ß1-induced cells were analyzed for the function of NEAT1 in PF progression. qRT-PCR or Western blot was applied to detect NEAT1, miR­9-5p or protein expressions. PF mice model assay was used to detect the effects of NEAT1 on PF in vivo. Luciferase reporter assay was applied to confirm target relationship between NEAT1 and miR­9-5p. Correlation of NEAT1 and miR-9-5p was analyzed by Spearman's method. RESULTS: We observed that NEAT1 was significantly upregulated while miR-9-5p was downregulated in PF tissues and TGF-ß1-induced cells. A negative correlation was exhibited of NEAT1 and miR-9-5p expression in PF tissues. Protein level of p-Smad2 was increased in TGF-ß1 induced cells. Furthermore, NEAT1 knockdown increased E-cadherin expression, while decreased N-cadherin, Vimentin, Collagen I, Collagen III and α-smooth muscle actin (α-SMA) expressions in TGF-ß1-induced cells. Moreover, NEAT1 could directly target miR-9-5p to regulate the PF induced by TGF-ß1. The miR-9-5p overexpression inhibited TGF-ß1 and p-Smad2 expression, while NEAT1 overexpression attenuated this effect. In addition, NEAT1 inhibition enhanced E-cadherin expression, and reduced TGF-ß1, p-Smad2, N-cadherin, Collagen I, Collagen III, α-SMA and Vimentin expression after BLM treatment. CONCLUSIONS: Taken together, our findings showed that NEAT1 knockdown attenuated PF via the regulatory of miR-9-5p and TGF-ß signaling to repress EMT and might provide new therapeutic targets for PF patients.

Adiponectin attenuates endoplasmic reticulum stress and alveolar epithelial apoptosis in COPD rats.

OBJECTIVE: The present study was designed to evaluate the effect of Adiponectin (APN) against alveolar epithelial apoptosis in chronic obstructive pulmonary disease (COPD) rat models. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley (SD) rats were randomly assigned to three groups: Sham group, COPD group, and COPD + APN group (2.5 ug/kg/day). To assess the effect of APN, histopathological evaluations, lung function, and the apoptotic index (AI) of alveolar septal cells, were performed. In addition, the levels of oxidative stress and endoplasmic reticulum stress were measured. RESULTS: HE staining demonstrated that APN inhibited pathological injury in COPD rats. In addition, APN could restore the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum. APN also inhibited the levels of endoplasmic reticulum stress pathway including CHOP, phospho-JNK and Caspase-12 in alveolar epithelial cell. Furthermore, APN significantly inhibited the protein levels of Caspase-3 and apoptosis in alveolar epithelial cell of COPD rats. CONCLUSIONS: Our findings suggested that APN might effectively ameliorate the progression of COPD via inhibiting the endoplasmic reticulum stress-induced alveolar epithelial apoptosis in rats.

MIP-1α and NF-κB as indicators of acute kidney injury secondary to acute lung injury in mechanically ventilated patients.

OBJECTIVE: In this study the levels of macrophage inflammatory protein-1α and NF-κB were measured in patients suffering acute kidney injury secondary to acute lung injury induced by mechanical ventilation and in controls, to determine whether they are differentially expressed. PATIENTS AND METHODS: 160 patients were enrolled in our study: 40 had acute kidney injury secondary to acute lung injury induced by mechanical ventilation (group A), 40 had acute lung injury induced by mechanical ventilation, but no secondary acute kidney injury (group B), 40 were treated with mechanical ventilation but suffered no complications (group C), and 40 were treated with a conventional nasal catheter or oxygen mask inhalation (group D). The seric levels of MIP-1α, NF-κB and hs-CRP were compared amongst the groups at time points of 6, 12, 24, and 72 hours and at 7 days after the start of the respiratory treatment. RESULTS: The serum levels of MIP-1α, NF-κB and hs-CRP of groups A and B were significantly higher than those of groups C and D at each time point. Also, group A had higher levels than group B at each time point, and the differences were statistically significant (p < 0.05). No statistically significant differences were found while comparing levels in group C with those of group D (p > 0.05). In groups A and B, the levels of MIP-1α increased gradually to a peak at 72 hours and then fell again on the 7th day. Levels of NF-κB in groups A and B significantly increased at 6, 12 and 24 hours, and reached a peak level at 24 h, to then fall after 72 h. The levels in group A fell back to baseline at 7 days, while group B levels fell back to baseline faster, at 72 h. Finally, the levels of hs-CRP in groups A and B kept increasing even after 7 days. CONCLUSIONS: Based on these results, it is possible that the levels of MIP-1α and NF-κB be used as early indicators of inflammation reflecting the occurrence of acute kidney injury secondary to acute lung injury induced by mechanical ventilation.