Dataset Information

LncRNA GAS5 inhibits NLRP3 inflammasome activation-mediated pyroptosis in diabetic cardiomyopathy by targeting miR-34b-3p/AHR.

ABSTRACT: Long noncoding RNA GAS5 is down-regulated in cardiomyocytes in diabetic cardiomyopathy (DCM). Here, we studied the involvement of GAS5 in DCM by analyzing its expression in DCM mouse model and cardiac muscle cell line (HL-1 cells). Compared with normal mice, GAS5 was severely down-regulated in heart tissues of DCM mice. GAS5 overexpression improved cardiac function and myocardial hypertrophy in DCM mice. In addition, the expression of NLRP3, caspase-1, Pro-caspase-1, IL-1β and IL-18 were increased in heart tissues of DCM mice and high glucose-treated HL-1 cells, which was repressed by GAS5 up-regulation. GAS5 overexpression suppressed caspase-1 activity, LDH release and the levels of IL-1β, IL-18 in the high glucose-treated HL-1 cells. Moreover, GAS5 regulated AHR expression by sponging miR-34b-3p. Furthermore, GAS5 overexpression suppressed NLRP3 inflammasome activation-mediated pyroptosis by regulating miR-34b-3p/AHR axis. In summary, our study demonstrates that GAS5 acts as a competing endogenous RNA to enhance AHR expression by sponging miR-34b-3p, which consequently represses NLRP3 inflammasome activation-mediated pyroptosis to improve DCM. Thus, our data provide a novel lncRNA GAS5 that could be a valuable target for DCM treatment.

SUBMITTER: Xu Y

PROVIDER: S-EPMC7714483 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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LncRNA GAS5 inhibits NLRP3 inflammasome activation-mediated pyroptosis in diabetic cardiomyopathy by targeting miR-34b-3p/AHR.

Xu Yingying Y Fang Haiyang H Xu Qin Q Xu Congcong C Yang Lu L Huang Chahua C

Cell cycle (Georgetown, Tex.) 20201023 22

Long noncoding RNA GAS5 is down-regulated in cardiomyocytes in diabetic cardiomyopathy (DCM). Here, we studied the involvement of GAS5 in DCM by analyzing its expression in DCM mouse model and cardiac muscle cell line (HL-1 cells). Compared with normal mice, GAS5 was severely down-regulated in heart tissues of DCM mice. GAS5 overexpression improved cardiac function and myocardial hypertrophy in DCM mice. In addition, the expression of NLRP3, caspase-1, Pro-caspase-1, IL-1β and IL-18 were increas ...[more]

PMID: 33092444

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Project description:Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses a spectrum of diseases, including chronic obstructive bronchitis and emphysema. Pyroptosis is a unique form of inflammatory cell death mediated by the activation of caspase‑1 and inflammasomes. The long non‑coding RNA (lncRNA) growth arrest‑specific 5 (GAS5) is a well‑documented tumor suppressor, which is associated with cell proliferation and death in various diseases. The aim of the present study was to evaluate whether lncRNA GAS5 is associated with the pyroptosis in COPD. To create a COPD cell model, MRC‑5 cells were treated with 10 µg/ml lipopolysaccharide (LPS) for 48 h. Then the level of pro‑caspase 1, caspase 1, IL‑1β, IL‑18, NLRP3 and cleaved gasdermin D (GSDMD) was examined by western blotting. GAS5 mRNA level was detected by qualitative PCR following LPS treatment in MRC‑5 cells. Subsequently, IL‑2, IL‑6, IL‑10 and TNF‑α in MRC‑5 cells was measured by ELISA. Then the proliferation ability of MRC‑5 cells was detected by CCK‑8. Cell death was detected by TUNEL assay. LDH release was measured using an LDH Cytotoxicity Assay kit. The Magna RIP kit was used to validate the interaction between GAS5 and miR‑223‑3p. The present study revealed that increased expression levels of caspase‑1, IL‑1β, IL‑18 and cleaved GSDMD were observed in LPS‑treated MRC‑5 cells, indicating that pyroptosis is involved in COPD progression. Additionally, LPS induced the increase in GAS5 mRNA expression levels and the release of inflammatory factors (IL‑2, IL‑6, IL‑10 and TNF‑α), suggesting that GAS5 is implicated in pyroptosis in COPD. Furthermore, upregulation of GAS5 promoted cell death and inhibited proliferation in the MRC‑5 cell line. Additionally, increased GAS5 expression significantly promoted the production of caspase‑1, IL‑1β, IL‑18, cleaved GSDMD and NLR pyrin domain containing protein 3 (NLRP3). A dual‑luciferase assay demonstrated that GAS5 could directly bind to microRNA‑223‑3p (miR‑223‑3p), and NLRP3 is a direct target of miR‑223‑3p. Furthermore, GAS5 reduced the expression levels of miR‑223‑3p, while it increased the expression levels of NLRP3. The present study concluded that lncRNA GAS5 promoted pyroptosis in COPD by targeting the miR‑223‑3p/NLRP3 axis, implying that GAS5 could be a potential target for COPD.

Dataset Information

LncRNA GAS5 inhibits NLRP3 inflammasome activation-mediated pyroptosis in diabetic cardiomyopathy by targeting miR-34b-3p/AHR.

Publications

LncRNA GAS5 inhibits NLRP3 inflammasome activation-mediated pyroptosis in diabetic cardiomyopathy by targeting miR-34b-3p/AHR.

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