MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS. miR-223−/+ mice exhibited more severe ALI and cytokine dysregulation. Other studies have shown that MTD-induced increases in miR-223 expression are mainly contributed by Ly6G+ neutrophils from the haematopoietic system. miR-223 blocks bone marrow-derived Ly6G+ neutrophil differentiation and inhibits peripheral cytokine release. In addition, MTD-induced miR-223 expression activates a negative feedback pathway that targets the inhibition of NLRP3 expression and IL-1β release; therefore, miR-223 deficiency can lead to the sustained activation of NLRP3-IL-1β. Finally, elimination of peripheral Ly6G+ neutrophils and pharmacological blockade of the miR-223–NLRP3–IL-1β signalling axis could alleviate MTD-induced ALI. In summary, miR-223 is essential for regulating the pathogenesis of DAMP-induced ALI.

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Acute myocardial infarction (MI) is the leading cause of sudden death worldwide. MicroRNAs (miRs)is a novel class of regulators of cardiovascular diseases such as MI. This study aimed to explore the role of miR-98 in MI and its underlying mechanisms. We found that miR-98 was downregulated both in infarcted and ischemic myocardium of MI mice as well as H 2 O 2 -treated neonatal rat ventricular myocytes (NRVCs). miR-98 overexpression remarkably increased cell viability and inhibited apoptosis of H 2 O 2 -treated NRVCs. Meanwhile, overexpression of miR-98 reversed H 2 O 2 -induced Bcl-2 downregulation and Bax elevation and significantly reduced JC-1 monomeric cells. Meanwhile, miR-98 overexpression attenuated the upregulation of Fas and caspase-3 in H 2 O 2 -treated cardiomyocytes at the mRNA and protein levels. Dual-luciferase reporter assay showed that miR-98 directly targeted to Fas 3′-UTR. Furthermore, MI mice injected with miR-98-agomir had a significant reduction of apoptotic cells, the serum LDH levels, myocardial caspase-3 activity, Fas and caspase-3 expression in heart tissues. Administration of miR-98-agomir also showed decreased infarct size and improved cardiac function. Collectively, miR-98 is downregulated in the MI heart and NRVCs in response to H 2 O 2 stress, and miR-98 overexpression protects cardiomyocytes against apoptosis. Anti-apoptotic effects of miR-98 are associated with regulation of Fas/Caspase-3 apoptotic signal pathway.Acute myocardial infarction (AMI), resulting from coronary artery occlusion, is the most common causes of cardiovascular morbidity and mortality worldwide 1 . Apoptosis, which is triggered by an imbalance between proand anti-apoptotic factors, is frequently detected in ischemic heart tissue 2 . Cardiomyocyte apoptotic death in the border area close to myocardial infarcted area leads to cardiomyocyte loss, aggravates cardiac dysfunction and even causes heart failure and mortality 3,4 . Therefore, targeting inhibition of cardiomyocytes apoptosis during early stage of MI is critical for reducing infarct size and promoting cardiac repair, which is a key approach for treating ischemic heart disease. However, the molecular components regulating AMI-induced apoptosis in cardiomyocytes remain poorly understood.MicroRNAs (miRNAs) are a group of small, endogenous and non-coding RNA molecules, with about 22 nucleotides in length, which has been shown to post-transcriptionally regulate the expression of target genes, leading to the destruction and degeneration of mRNAs 5 . Clinical trials and animal experiments indicate that miRNAs are potential biomarkers and therapeutic targets for cardiac ischemia 6,7 . Moreover, several miRNAs are implicated in playing regulatory roles in cardiomyocytes apoptosis. Recent studies elucidate that miR-21, -24, -133, -210, -494 and -499 prevent myocytes against ischemia/reperfusion-induced apoptosis, while miR-1, -29, -195, -199a, -497 and -320 promote apoptosis [8][9][10] . Our previous study has also shown that combination of miR-21 and miR-146a h...

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