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Updated: Jul 20, 2025
A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
Published on: January 20, 2023
[Sinomenine ameliorates bleomycin A5-induced pulmonary fibrosis by blocking the miR-21/ADAMTS-1 signaling pathway in
Lijing Liu1, Hong Qian2, Qingxin Meng2
1Department of Clinical Medicine, School of Medicine, Changsha Social Work College, Changsha 410004; Department of Respiratory and Critical Care Medicine, First People's Hospital of Huaihua, The Fourth Affiliated Hospital of Jishou University, Huaihua 418000, China.
Abstract:
Objective To explore the impact of sinomenine on bleomycin A5-induced pulmonary fibrosis (PF) in rats and the underlying mechanism. Methods MRC-5 cells were cultured and treated with sinomenine to determine its optimal concentration and time through the MTT assay. Subsequently, MRC-5 cells were incubated with 80 μmol/L sinomenine for 48 hours or transfected with miR-21 mimic/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) siRNA prior to sinomenine treatment. The expression of miR-21, ADAMTS-1, collagen type 1 (Col1) and collagen type 3 (Col3) was detected by quantitative real-time PCR (qRT-PCR) and/or Western blot analysis. Thirty SD rats were randomly divided into control group, sinomenine group and sinomenine combined with miR-21 agomir group, with 10 animals in each group. Bleomycin A5 were intratracheally administered to establish the PF model. Then, rats in control group, sinomenine group and sinomenine +miR-21 agomir group were treated with 9 g/L sodium chloride solution, sinomenine and sinomenine+miR-21 agomir, respectively. On day 28, all rats were sacrificed. HE and Masson staining was performed in pulmonary tissue. The expression of ADAMTS-1, Col1 and Col3 in pulmonary tissue were detected by qRT-PCR and/or Western blot analysis. ELISA was used to measure serum procollagen type 1 carboxyterminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) levels. Results Administration of sinomenine decreased miR-21 levels, up-regulated ADAMTS-1 expression, and promoted Col1 and Col3 degradation in MRC-5 cells. Importantly, interfering with the miR-21/ADAMTS-1 signaling pathway partially reversed the promotive effect of sinomenine on Col1 and Col3 degradation. Treatment of SD rats with sinomenine reduced alveolitis and PF scores, decreased serum P1CP and P3NP levels, up-regulated pulmonary ADAMTS-1 expression, and down-regulated Col1 and Col3 expression. However, these effects were reversed by miR-21 agomir. Conclusion Sinomenine promotes Col1 and Col3 degradation and inhibits PF in rats by miR-21/ADAMTS-1 pathway.
Insights
Sinomenine inhibits pulmonary fibrosis (PF) by downregulating miR-21 and upregulating ADAMTS-1, promoting collagen degradation. This pathway offers a potential therapeutic strategy for PF.
Area of Science:
- Pharmacology
- Cell Biology
- Pathology
Context:
- Pulmonary fibrosis (PF) is a severe lung disease characterized by excessive collagen deposition.
- Bleomycin A5-induced PF in rats is a common model for studying antifibrotic agents.
- The miR-21/ADAMTS-1 signaling pathway plays a crucial role in fibrotic processes.
Purpose:
- To investigate the antifibrotic effects of sinomenine in bleomycin A5-induced pulmonary fibrosis in rats.
- To elucidate the underlying mechanism involving the miR-21/ADAMTS-1 signaling pathway.
Summary:
- Sinomenine treatment in MRC-5 cells and rats with PF led to decreased miR-21 expression and increased ADAMTS-1 expression.
- Sinomenine promoted the degradation of collagen type 1 (Col1) and collagen type 3 (Col3) in both in vitro and in vivo models.
- Interference with the miR-21/ADAMTS-1 pathway partially reversed the antifibrotic effects of sinomenine.
Impact:
- Sinomenine demonstrates potential as a therapeutic agent for pulmonary fibrosis.
- The study highlights the miR-21/ADAMTS-1 pathway as a key target for antifibrotic therapies.
- Findings provide insights into the molecular mechanisms of sinomenine's action against PF.
