miR‑351‑5p aggravates lipopolysaccharide‑induced acute lung injury via inhibiting AMPK

Abstract

Inflammation and oxidative stress have indispensable roles in the development of acute lung injury (ALI). MicroRNA (miRNA/miR)-351-5p was initially identified as a myogenesis-associated miRNA; however, its role in lipopolysaccharide (LPS)-induced ALI remains unclear. The aim of the present study was to investigate the role and potential mechanisms of miR-351-5p in ALI. ALI was induced through a single intratracheal injection of LPS for 12 h, and miR-351-5p agomir, antagomir or their corresponding negative controls were injected into the tail vein before LPS stimulation. Compound C, 2' ,5'-dideoxyadenosine and H89 were used to inhibit AMP-activated protein kinase (AMPK), adenylate cyclase and protein kinase A (PKA), respectively. miR-351-5p levels in the lungs were significantly increased in response to LPS injection. miR-351-5p antagomir alleviated, while miR-351-5p agomir aggravated LPS-induced oxidative stress and inflammation in the lungs. The present results also demonstrated that miR-351-5p antagomir attenuated LPS-induced ALI via activating AMPK, and that the cAMP/PKA axis was required for the activation of AMPK by the miR-351-5p antagomir. In conclusion, the present study indicated that miR-351-5p aggravated LPS-induced ALI via inhibiting AMPK, suggesting that targeting miR-351-5p may help to develop efficient therapeutic approaches for treating ALI.

Emerging Role of cAMP/AMPK Signaling

“…MicroRNAs (miRs) are also involved in inflammatory responses. In a mouse model of lipopolysaccharide-induced acute lung injury, Hu et al [ 101 ] showed an upregulation of miR351-5p that was accompanied by suppression of cAMP/PKA and AMPK signaling. Administration of an antagomir to miR351-5p abrogated this lipopolysaccharide-induced suppression of cAMP/PKA and AMPK signaling, resolved inflammation, and improved mouse survival [ 101 ].…”

“…In a mouse model of lipopolysaccharide-induced acute lung injury, Hu et al [ 101 ] showed an upregulation of miR351-5p that was accompanied by suppression of cAMP/PKA and AMPK signaling. Administration of an antagomir to miR351-5p abrogated this lipopolysaccharide-induced suppression of cAMP/PKA and AMPK signaling, resolved inflammation, and improved mouse survival [ 101 ]. However, the mechanism of the miR351-5p-mediated suppression of cAMP signaling was not investigated, although the mRNAs of adenylyl cyclase 1 (Adcy1), Adcy5, and Adcy6 contain seed binding sites for miR351-5p in 3′-UTR regions [ 101 ], indicating potential downregulation of tmAC expression.…”

MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1

“…More interestingly, PM2.5 can alter the expression of micro ribonucleic acids (miRNAs) in the body [ 15 ]. In the present study, a differentially expressed gene miR-217-5p was found through GEO database and bioinformatics analysis, and the JAK-STAT signaling pathways were enriched pathways.…”

Preclinical evidence using synthetic compounds and natural products indicates that AMPK represents a potential pharmacological target for the therapy of pulmonary diseases

“…91 Some compounds can also inhibit inflammation and oxidative stress through AMPK activation in LPS-induced ALI in mice, such as MOTS-c (a mitochondrial-derived peptide), 81 and the microRNAs (miRNAs) small noncoding RNA molecules miR-351-5p, and miR-31-5p antagomirs. 103,104 Mogroside IIIE, extracted from Siraitia grosvenorii, is a cucurbitane-type compound that inhibits NO release, with antifibrotic activity. It alleviated the lung injury and inflammatory response and inhibited the upregulation of mRNA and protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and inflammatory factor high mobility group box 1(HMGB1) as well as the phosphorylation levels of mitogen-activated protein kinases (MAPKs) (JNK, ERK, and p38), IκBα and NF-κB in lung tissue of LPS-induced ALI mice.…”

“…AMPK/Nrf2 is also involved in the DHE‐mediated suppression of the methicillin‐resistant Staphylococcus aureus (MRSA)‐induced M1/M2 macrophage ratio and alleviation of oxidative stress and inflammation in MRSA‐induced ALI mice 91 . Some compounds can also inhibit inflammation and oxidative stress through AMPK activation in LPS‐induced ALI in mice, such as MOTS‐c (a mitochondrial‐derived peptide), 81 and the microRNAs (miRNAs) small noncoding RNA molecules miR‐351‐5p, and miR‐31‐5p antagomirs 103,104 …”