LncRNA KCNQ1OT1 Participates in Ox-LDL-Induced Proliferation/Apoptosis Imbalance in Vascular Smooth Muscle Cells by Regulating the MiR-196a-5p/FOXO1 Axis.

Backgroud The present study aimed to investigate the function and regulatory mechanisms of lncRNA KCNQ1OT1 in vascular smooth muscle cells under oxidation low lipoprotein stimulation. Methods RNA sequencing was used to detect transcriptome changes of vascular smooth muscle cells treated with oxidation low lipoprotein. KCNQ1OT1, miR-196a-5p, and FOXO1 expression levels in VSMCs after oxidation low lipoprotein treatment were assessed using qRT-PCR and western blotting. RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay were used to confirm the interaction among lncRNA KCNQ1OT1, miR-196a-5p, and FOXO1. The functions of KCNQ1OT1, miR-196a-5p, and FOXO1 were analyzed by CCK-8 and flow cytometry. The serum samples of high fat-feeding mice and atherosclerosis patients were collected, and the levels of KCNQ1OT1 and miR-196a-5p were analyzed. Results In vitro expression of KCNQ1OT1 and FOXO1 decreased in VSMCs treated with oxidation low lipoprotein, accompanied by overexpression of miR-196a-5p. As a ceRNA, KCNQ1OT1 positively regulated FOXO1 and imparted a negative regulatory effect on miR-196a-5p. Interference KCNQ1OT1/miR-196a-5p/FOXO1 could change roliferation/apoptosis imbalance in VSMCs under oxidation low lipoprotein stimulation. Higher levels of KCNQ1OT1 and lower levels of miR-196a-5p can be found in the thoracic aorta tissues of high fat-feeding mice and serum samples from individuals with carotid atherosclerosis. Conclusion Aberrant expression of KCNQ1OT1/miR-196a-5p/FOXO1 pathway mediated oxidation low lipoprotein-induced proliferation/apoptosis imbalance in VSMCs.

The protective effects of propofol against renal ischemia-reperfusion injury are potentiated by norisoboldine treatment via inhibition of oxidative stress pathways.

Acute kidney injury (AKI) is a significant worldwide health problem. The protective effects of norisoboldine (NOR) against ischemia/reperfusion (I/R) induced renal injury in a rat model were evaluated. AKI was induced in rats by I/R. Animals were treated with 20 mg/kg/h propofol, intraperitoneally administered and 10 mg/kg NOR 30 min before inducing renal ischemia. Biomarkers of kidney function, including cytokines and oxidative stress parameters, were measured in serum. The serum levels of creatinine and blood urea nitrogen in propofol- and NOR-treated rats were lower compared to the untreated I/R group. Moreover, treatment with propofol or NOR, alone and in combination, decreased the levels of cytokines and oxidative stress in rats with kidney injury. In conclusion, this study suggested that treatment with NOR potentiated the nephroprotective effects of propofol in rats with I/R-induced renal injury by ameliorating oxidative stress and apoptosis pathway.

Dexmedetomidine targets miR-146a and participates in the progress of chronic obstructive pulmonary disease in vivo and in vitro.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease and the third leading cause of death in the world. Dexmedetomidine has been reported to effectively inhibit histamine-induced bronchoconstriction. However, the molecular mechanism of dexmedetomidine in COPD has not been found. OBJECTIVE: To explore the role and mechanism of dexmedetomidine in COPD, and to provide theoretical basis for clinical treatment of COPD. METHODS: The expression of miR-146a was regulated by mimics or inhibitor and the relative expression of apoptotic proteins p53, Bax and Bcl-2 in human bronchial epithelial 16HBE cells was determined by real-time PCR and Western blot. Dexmedetomidine was treated for 16HBE cells and alveolar epithelial type II cells (AEC2), the cell apoptosis was detected by TUNEL and Hoechst33342 staining. A COPD rat model was established by smoking to test the effects of dexmedetomidine on the progression of COPD. The levels of IL-6, IL-1ß and TNF-α in serum were measured by ELISA and the protein concentration of bronchoalveolar lavage fluid (BALF) was also detected in dexmedetomidine treated COPD rat model. RESULTS: miR-146a promoted 16HBE cell apoptosis and reduced cell proliferation. Additionally, dexmedetomidine was showed to reduce the 16HBEL cell apoptosis through reducing the expression of miR-146a. Moreover, dexmedetomidine regulated cell apoptosis and cell apoptosis through miR-146a in AEC2 cells. More importantly, dexmedetomidine attenuated the morphology and pathology of COPD rat model. CONCLUSION: Dexmedetomidine reduced 16HBE cells and AEC2 cell apoptosis and attenuated COPD by down-regulating miR-146a.

The MicroRNA-210/Casp8ap2 Pathway Alleviates Hypoxia-Induced Injury in Myocardial Cells by Regulating Apoptosis and Autophagy.

AIM: This study was conducted to investigate the role of the miR-210/Caspase8ap2 pathway in apoptosis and autophagy in hypoxic myocardial cells. METHODS: The miR-control, miR-210 mimic, and miR-210 inhibitor were transfected into rat myocardial H9C2 cells. The transfection efficiency of exogenous miR-210 was determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). H9C2 cells were then treated with CoCl2 for 24, 48, and 72 h to generate a myocardial injury model. The apoptosis of H9C2 cells was assessed by flow cytometry. Additionally, a western blot assay was used to determine the expression of the autophagy-associated proteins light chain 3 (LC3), p62 and Beclin-1, and apoptosis-associated proteins Caspase8ap2, cleaved caspase 8, and cleaved caspase 3. RESULTS: We determined that a 48 h hypoxia treatment duration in H9C2 cardiomyocytes induced myocardial injury. Additionally, the overexpression of miR-210 significantly inhibited cell apoptosis. MiR-210 suppressed autophagy by upregulating p62 and downregulating LC3II/I in hypoxic H9C2 cells. Caspase8ap2 was a putative target of miR-210, miR-210 mediated apoptosis, and autophagy of H9C2 cells via suppressing Caspase8ap2. Furthermore, the expression of caspase 8, caspase 3, and Beclin-1 were decreased in response to miR-210. CONCLUSION: miR-210 exhibits anti-apoptosis and anti-autophagy effects, which alleviate myocardial injury in response to hypoxia.

MiR-29a in mesenchymal stem cells inhibits FSTL1 secretion and promotes cardiac myocyte apoptosis in hypoxia-reoxygenation injury.

BACKGROUND: Mesenchymal stem cells (MSCs) are under consideration for myocardial ischemia-reperfusion (I/R) injury therapy, but their mechanism remains to be evaluated. In this article, we aimed to study the effects of the miR-29a/follistatin-like 1 axis in bone marrow-derived mesenchymal stem cells on modulating myocyte apoptosis after hypoxia-reoxygenation (H/R) injury. METHODS: An in vitro myocardial ischemia-reperfusion injury model of H9c2 cells was developed by hypoxia-reoxygenation injury. The mRNA levels of follistatin-like 1, Bcl-2, Bax, and miR-29a and the protein levels of Bcl-2, Bax, cleaved caspase-3, and components of the JAK2/STAT3 pathway were detected by qRT-PCR and western blotting, respectively. Secretion of follistatin-like 1 was evaluated by enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by flow cytometry. The interaction between miR-29a and follistatin-like 1 was evaluated by dual luciferase reporter assay. RESULTS: MiR-29a suppressed the expression and secretion of follistatin-like 1 in bone marrow-derived mesenchymal stem cells. Overexpression of follistatin-like 1 in bone marrow-derived mesenchymal stem cells decreased apoptosis of myocytes induced by hypoxia-reoxygenation. Cell apoptosis in myocytes was promoted by conditioned medium from bone marrow-derived mesenchymal stem cells with ectopic miR-29a expression. Conditioned medium of miR-29a-overexpressing bone marrow-derived mesenchymal stem cells inhibited the JAK2/STAT3 pathway in myocytes to promote apoptosis of myocytes. CONCLUSIONS: MiR-29a in bone marrow-derived mesenchymal stem cells inhibits follistatin-like 1 secretion and promotes myocyte apoptosis by suppressing the JAK2/STAT3 pathway in hypoxia-reoxygenation injury.