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circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury
Jiang Zhu1, Fukuan Zhong1, Futao Chen1
1Department of Respiratory, The Second People's Hospital of Lianyungang, Lianyungang 222023, Jiangsu, China.
Abstract:
Acute lung injury (ALI) is a respiratory disorder characterized by acute respiratory failure. circRNA mus musculus (mmu)-circ_0001679 was reported overexpressed in septic mouse models of ALI. Here the function of circ_0001679 in sepsis-induced ALI was investigated. In vitro models and animal models with ALI were, respectively, established in mouse lung epithelial (MLE)-12 cells and C57BL/6 mice. Pulmonary specimens were harvested for examination of the pathological changes. The pulmonary permeability was examined by wet-dry weight (W/D) ratio and lung permeability index. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the bronchoalveolar lavage fluid (BALF), the lung tissues, and the supernatant of MLE-12 cells were measured by enzyme linked immunosorbent assay . Apoptosis was determined by flow cytometry. Bioinformatics analysis and luciferase reporter assay were used to assess the interactions between genes. We found that circ_0001679 was overexpressed in lipopolysaccharide (LPS)-stimulated MLE-12 cells. circ_0001679 knockdown suppressed apoptosis and proinflammatory cytokine production induced by LPS. Moreover, circ_0001679 bound to mmu-miR-338-3p and miR-338-3p targeted dual-specificity phosphatases 16 (DUSP16). DUSP16 overexpression reversed the effect of circ_0001679 knockdown in LPS-stimulated MLE-12 cells. Furthermore, circ_0001679 knockdown attenuated lung pathological changes, reduced pulmonary microvascular permeability, and suppressed inflammation in ALI mice. Overall, circ_0001679 knockdown inhibits sepsis-induced ALI progression through the miR-338-3p/DUSP16 axis.
Insights
Circular RNA (circRNA) mmu-circ_0001679 promotes sepsis-induced acute lung injury (ALI). Knocking down this circRNA reduces inflammation and apoptosis, offering a potential therapeutic target for ALI treatment.
Area of Science:
- Molecular Biology
- Immunology
- Respiratory Medicine
Background:
- Acute lung injury (ALI) is a critical respiratory condition often caused by sepsis, leading to acute respiratory failure.
- Circular RNA (circRNA) mmu-circ_0001679 has been observed to be overexpressed in sepsis-induced ALI models.
- Understanding the specific role of circ_0001679 in ALI pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the functional role of circ_0001679 in the development of sepsis-induced ALI.
- To elucidate the underlying molecular mechanism, including gene interactions and signaling pathways.
- To evaluate the therapeutic potential of targeting circ_0001679 in ALI.
Main Methods:
- Establishment of in vitro (MLE-12 cells) and in vivo (C57BL/6 mice) models of ALI induced by lipopolysaccharide (LPS).
- Assessment of lung pathology, pulmonary permeability (W/D ratio, lung permeability index), inflammatory cytokine levels (TNF-α, IL-6, IL-1β) via ELISA, and apoptosis via flow cytometry.
- Bioinformatics analysis and luciferase reporter assays to determine the interaction between circ_0001679, miR-338-3p, and DUSP16.
Main Results:
- circ_0001679 was found to be significantly overexpressed in LPS-stimulated MLE-12 cells.
- Knockdown of circ_0001679 effectively suppressed LPS-induced apoptosis and the production of pro-inflammatory cytokines.
- circ_0001679 directly binds to mmu-miR-338-3p, which in turn targets DUSP16. DUSP16 overexpression reversed the protective effects of circ_0001679 knockdown.
- In vivo, circ_0001679 knockdown attenuated lung injury, reduced pulmonary microvascular permeability, and suppressed inflammation in ALI mice.
Conclusions:
- circ_0001679 plays a pro-inflammatory and pro-apoptotic role in sepsis-induced ALI.
- The mechanism involves the circ_0001679/miR-338-3p/DUSP16 axis.
- Targeting circ_0001679 represents a promising therapeutic strategy for inhibiting the progression of sepsis-induced ALI.
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