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

GND
1301514500
Affiliation
Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany.
Jansing, Johanna Christine;
GND
1014757525
ORCID
0000-0002-8855-2883
Affiliation
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, 30625 Hannover, Germany.
Fiedler, Jan;
GND
1017330581
ORCID
0000-0001-8444-0940
Affiliation
Institute of Toxicology, Hannover Medical School, 30625 Hannover, Germany.
Pich, Andreas;
GND
1114422789
ORCID
0000-0003-4967-0702
Affiliation
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, 30625 Hannover, Germany.
Viereck, Janika;
GND
123268605
ORCID
0000-0003-4360-1511
Affiliation
Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, 30625 Hannover, Germany.
Thum, Thomas;
GND
129323667
ORCID
0000-0002-7827-4867
Affiliation
Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany.
Mühlfeld, Christian;
GND
1116500035
Affiliation
Institute of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany.
Brandenberger, Dora Christina

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.

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