miR-21-KO Alleviates Alveolar Structural Remodeling and Inflammatory Signaling in Acute Lung Injury

Abstract

Acute lung injury (ALI) is characterized by enhanced permeability of the air–blood barrier, pulmonary edema, and hypoxemia. MicroRNA-21 (miR-21) was shown to be involved in pulmonary remodeling and the pathology of ALI, and we hypothesized that miR-21 knock-out (KO) reduces injury and remodeling in ALI. ALI was induced in miR-21 KO and C57BL/6N (wildtype, WT) mice by an intranasal administration of 75 µg lipopolysaccharide (LPS) in saline (n = 10 per group). The control mice received saline alone (n = 7 per group). After 24 h, lung function was measured. The lungs were then excised for proteomics, cytokine, and stereological analysis to address inflammatory signaling and structural damage. LPS exposure induced ALI in both strains, however, only WT mice showed increased tissue resistance and septal thickening upon LPS treatment. Septal alterations due to LPS exposure in WT mice consisted of an increase in extracellular matrix (ECM), including collagen fibrils, elastic fibers, and amorphous ECM. Proteomics analysis revealed that the inflammatory response was dampened in miR-21 KO mice with reduced platelet and neutrophil activation compared with WT mice. The WT mice showed more functional and structural changes and inflammatory signaling in ALI than miR-21 KO mice, confirming the hypothesis that miR-21 KO reduces the development of pathological changes in ALI.

Mechanisms of interactions between lung‐origin telocytes and mesenchymal stem cells to treat experimental acute lung injury

“…Mice were anesthetized with Isoflurane in a plastic box with controlled ventilation and put in a supine position of head‐up on the board tilted at 30°. LPS at 1000 μg/mL was intratracheally administered to mice at a volume of 1 mL/kg mice body weight (BW) 16 . Animals for controls received the same manipulations and volume of PBS at 1 mL/kg BW.…”

“…LPS at 1000 μg/mL was intratracheally administered to mice at a volume of 1 mL/kg mice body weight (BW). 16 Animals for controls received the same manipulations and volume of PBS at 1 mL/kg BW. Mice remained in the position until regaining of consciousness and then had access to food and water ad libitum.…”

Inhibition of miR-21 ameliorates LPS-induced acute lung injury through increasing B cell lymphoma-2 expression

“…18 Consistent with our results, Jansing et al demonstrated that miR-21 knock-out alleviated alveolar structural remodelling and inflammatory signalling in ALI. 10 Therefore, miR-21 may exert its roles depending on different cell types and species.…”

“…7,8 In addition, miRNAs have been identified to be upregulated in inflammatory conditions, such as miR-155 9 and miR-21. 10 Jansing et al demonstrated that inflammatory reactions were impaired in miR-21 knock-out mice with reduced platelet and neutrophil activation compared to wild type (WT) mice that showed inflammatory and pathological changes in the presence of LPS. 10 However, more in vitro assays and in vivo experiments should be explored to elucidate the mechanisms underlying miR-21-involved ALI.…”

AntagomiRs: A novel therapeutic strategy for challenging COVID-19 cytokine storm

“…Another evidence in favour of the association between miRNAs and inflammatory cytokines was seen for miR-21, an oncogene, profibrotic molecule that, at least in murine models, was seen to be associated with acute inflammatory processes at the lung level mediated by the classic “triad” of pro-inflammatory cytokines, IL-1β, IL-6, TNF-α [ 8 , 9 ]. Besides, it was also seen that its upregulation increases the expression of IL-8 and tumorigenesis in airway epithelial cells exposed to cigarette smoke [ 10 ].…”