Long noncoding RNA MALAT1 inhibition attenuates sepsis‐induced acute lung injury through modulating the miR‐129‐5p/PAX6/ZEB2 axis

Abstract

This research aimed to investigate the role of the long noncoding RNA metastasisassociated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-129-5p (miR-129-5p)/paired box gene 6 (PAX6) axis in sepsis-induced acute lung injury (ALI). MLE-12 cells and C57BL/6 mice were induced by LPS to establish lung injury in in vitro and in vivo models. Cell viability and apoptosis were measured by cell counting kit-8 assay and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Levels of inflammatory cytokines in cell supernatants and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Lung injury was evaluated by lung wet weight-to-dry weight ratio and hematoxylin-eosin staining. MALAT1, PAX6, and zinc finger E-box-binding homeobox 2 (ZEB2) expression was elevated and miR-129-5p expression was reduced in the serum of patients with sepsis-induced ALI, LPS-induced MLE-12 cells, and lung tissues of ALI mice. MALAT1 interference delayed the LPS-induced cell proliferation decrease, apoptosis increase, and inflammatory factor increase. miR-129-5p inhibition could reverse the delaying effect of MALAT1 interference on LPS-induced lung cell injury. PAX6 overexpression (oe) reversed the inhibitory effect of miR-129-5p oe on LPSinduced lung cell injury. Downregulating MALAT1 reduced pulmonary edema, inflammatory cytokine levels, lung injury, and apoptosis in ALI mice. Moreover, miR-129-5p suppression or PAX6 oe reversed the delaying effect of MALAT1 interference on sepsis-induced ALI. MALAT1 aggravates sepsis-induced ALI via the miR-129-5p/PAX6/ZEB2 axis.

Down‐regulating lncRNA KCNQ1OT1 relieves type II alveolar epithelial cell apoptosis during one‐lung ventilation via modulating miR‐129‐5p/HMGB1 axis induced pulmonary endothelial glycocalyx

“…Moreover, the role of miR-129-5p in LPS-induced AECII damage was also investigated. Different from the previous studies,41 miR-129-5p was revealed to protect lung endothelial or epithelial cells from LPS-induced injury by not only reducing the inflammation and apoptosis, but also alleviating the EG damage. Transfection of miR-129-5p mimics partially eliminated the damage of KCNQ1OT1 on LPS-induced AECIIs.…”

“…MiR‐129‐5p is reported to be involved in the acute lung injury 24,41 . Thus, we hypothesized that miR‐129‐5p was required in KCNQ1OT1‐meidated AECII injury.…”

“…MiR-129-5p is reported to be involved in the acute lung injury. 24,41 Thus, we hypothesized that miR-129-5p was required in KCNQ1OT1-meidated AECII injury. qRT-PCR results illustrated that KCNQ1OT1 was successfully up-regulated after the transfection of overexpression plasmids, while miR-129-5p mimics showed no significant impact on KCNQ1OT1 levels ( p < .001, Figure 6A).…”

Evaluation of the prognostic value of lncRNA UCA1 combined with extravascular lung water index and lung ultrasound score in patients with acute lung injury

“…LncRNA is commonly researched in human disorders, such as diseases of the respiratory system. LncRNA CASC2 is down‐regulated, lncRNA MALAT1 is up‐regulated, and lncRNA MIR3142HG is overexpressed in patients with ALI, indicating that their expression may be influenced by the occurrence of ALI 18–20 . The content of UCA1 is elevated and related to the disease severity and prognosis in patients with sepsis, which may become the cause of ALI 21 .…”

Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages

“…LncRNAs participate in various mechanisms involved in gene expression at multiple levels by interacting with RNA-binding proteins [ 16 ], DNA, and other RNA molecules [ 17 , 18 ]. In sepsis, lncRNAs regulate inflammation by acting as molecular scaffolds or decoys [ 19 , 20 ], influencing the expression of genes involved in inflammation [ 21 , 22 ], and modulating immune cell function and macrophage polarization [ 23 , 24 ]. LncRNAs can have both enhancing and suppressing effects on immune functions during sepsis [ 25 ], affecting the balance between pro-inflammatory and anti-inflammatory responses [ 26 , 27 , 28 ] and ultimately influencing the development of sepsis-associated organ dysfunction [ 22 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ].…”