Related Experiment Video
Updated: Feb 4, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
miR-423-5p/NDUFS7-mediated mitochondrial function modulation contributes to quercetin-induced attenuation of
Lang Xia1, Jing Cai2, Xueqin Zeng3
1GuiZhou University Medical College, Guiyang, 550025, Guizhou Province, China.
Background:
Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease that is critically influenced by epigenetic regulation and mitochondrial function during its pathogenesis and progression. Flavonoids possess significant anti-inflammatory and antioxidant properties, and among these compounds, quercetin has been shown to inhibit the progression of pulmonary fibrosis by modulating the expression of specific microRNAs (miRNAs) and alleviating oxidative stress associated with mitochondrial dysfunction. However, the precise underlying mechanism remains unclear.
Methods:
We established a murine model of pulmonary fibrosis via endotracheal nebulization with bleomycin, which resulted in uniformly distributed, severe fibrotic lesions in the lungs. Quercetin (Que) was administered via the intratracheal route, enabling targeted pulmonary delivery, reducing the required drug concentration, increasing bioavailability, and minimizing potential systemic toxicity. For the assessment of histopathological changes and collagen deposition in lung tissues, we used hematoxylin-eosin (H&E) and Masson's trichrome staining. In cell experiments, we stimulated A549 cells with transforming growth factor-β1 (TGF-β1) and transfected them with a miR-423-5p inhibitor to examine the expression levels of extracellular matrix (ECM) related proteins and the NDUFS7 subunit of mitochondrial complex I. Furthermore, we evaluated mitochondrial function by measuring reactive oxygen species (ROS) production, adenosine triphosphate (ATP) content, hydrogen peroxide (H2O2) levels, and the mitochondrial membrane potential.
Results:
Our research revealed that quercetin regulated the level of miR-423-5p in mouse lung tissue, as well as the expression of the mitochondrial complex I subunit NDUFS7. After 15 days of endotracheal nebulization with quercetin, extracellular matrix remodeling and collagen deposition in mouse lung tissue were alleviated, and the pulmonary fibrosis induced by bleomycin was improved. In vitro experiments demonstrated that inhibiting miR-423-5p enabled the normal translation and expression of NDUFS7, and improves mitochondrial function, ultimately alleviating the ECM remodeling induced by TGF-β1.
Conclusion:
Targeting miR-423-5p to modulate NDUFS7 expression represents a potential therapeutic strategy for ameliorating mitochondrial dysfunction and suppressing pulmonary fibrosis.
Insights
Quercetin alleviates pulmonary fibrosis by regulating miR-423-5p and NDUFS7, improving mitochondrial function. This suggests targeting miR-423-5p is a potential therapy for fibrosis and mitochondrial dysfunction.
Area of Science:
- Pulmonary Medicine
- Mitochondrial Biology
- Epigenetics
Background:
- Idiopathic pulmonary fibrosis (IPF) pathogenesis involves epigenetic regulation and mitochondrial dysfunction.
- Quercetin, a flavonoid, shows potential in inhibiting pulmonary fibrosis by modulating microRNAs (miRNAs) and oxidative stress.
- The exact mechanism of quercetin's action in pulmonary fibrosis remains unclear.
Purpose of the Study:
- To investigate the therapeutic effect of quercetin on bleomycin-induced pulmonary fibrosis in a murine model.
- To elucidate the role of miR-423-5p and NDUFS7 in quercetin's protective mechanism against pulmonary fibrosis.
- To assess the impact of quercetin on mitochondrial function and extracellular matrix remodeling.
Main Methods:
- Established a murine model of pulmonary fibrosis using bleomycin and administered quercetin intratracheally.
- Assessed lung histopathology and collagen deposition using H&E and Masson's trichrome staining.
- Conducted in vitro experiments with TGF-β1-stimulated A549 cells, including miR-423-5p inhibition, to analyze ECM proteins, NDUFS7 expression, and mitochondrial function (ROS, ATP, H2O2, membrane potential).
Main Results:
- Quercetin treatment in mice reduced miR-423-5p levels and modulated NDUFS7 expression, alleviating ECM remodeling and collagen deposition.
- In vitro, inhibiting miR-423-5p restored NDUFS7 expression and improved mitochondrial function, counteracting TGF-β1-induced ECM remodeling.
- Quercetin administration improved bleomycin-induced pulmonary fibrosis in mice.
Conclusions:
- Quercetin regulates miR-423-5p and NDUFS7 expression, thereby improving mitochondrial function and ameliorating pulmonary fibrosis.
- Targeting miR-423-5p to modulate NDUFS7 offers a potential therapeutic strategy for pulmonary fibrosis.
- This study highlights a novel mechanism involving miR-423-5p and mitochondrial complex I in fibrosis progression.
Related Concept Videos
01:42The Extracellular Matrix
01:29The Extracellular Matrix
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
01:26Extracellular Matrix
02:42Transcription Attenuation in Prokaryotes
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
02:54Nucleosome Remodeling
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
01:25Pulmonary Function Tests
Pulmonary Function Tests are crucial diagnostic tools for assessing respiratory function, particularly in patients with chronic respiratory disorders. They comprehensively evaluate lung volumes, ventilatory function, breathing mechanics, diffusion, and gas exchange. These tests help diagnose pulmonary diseases and play a significant role in monitoring disease progression, evaluating disability, and assessing response to therapy.
PFTs involve using a spirometer, a...