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[Nitric oxide modulates expression of matrix metalloproteinase in asthmatic rats]
Yiming Yuan1, Zengli Wang, Birong Dong
1Department of Geriatrics, The Huaxi Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To observe the effect of nitric oxide on expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in asthmatic rats.
Methods:
Thirty healthy male Wistar rats were randomly divided into control (n = 10), asthmatic (n = 10) and L-arginine (n = 10) groups. Lung tissues were sliced and stained with HE. The following morphometric parameters were measured by image analysis system: airway wall basement membrane perimeter (Pbm), total bronchial wall area (WAt), the inner wall area (WAi) and the area of smooth muscle (WAm). Levels of nitrites/nitrates and NOS activity in the lungs were measured by commercial NO and NOS kits. Transcriptional levels of MMP-2 and TIMP-1 mRNA in the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
Results:
(1) WAt/Pbm, WAi/Pbm and WAm/Pbm in the L-arginine group were (35.1 +/- 2.6) microm(2)/microm, (25.3 +/- 2.0) microm(2)/microm, and (8.7 +/- 1.5) microm(2)/microm, respectively. WAt/Pbm, WAi/Pbm and WAm/Pbm in the asthmatic group were (25.3 +/- 2.1) microm(2)/microm, (20.4 +/- 2.3) microm(2)/microm, and (4.2 +/- 2.0) microm(2)/microm, respectively. WAt/Pbm, WAi/Pbm and WAm/Pbm in the control group were (20.8 +/- 1.3) microm(2)/microm, (15.3 +/- 2.1) microm(2)/microm, and (3.1 +/- 1.1) microm(2)/microm, respectively. The differences among three groups were statistically significant. (2) Levels of nitrites/nitrates in the L-arginine group [(11.8 +/- 1.7) nmol/mg] and the asthmatic group [(7.2 +/- 2.1) nmol/mg] were significantly higher than that in the control group [(3.1 +/- 1.2) nmol/mg]. NOS activity in the lungs was (16.5 +/- 1.3) U/mg L-arginine group, (10.8 +/- 1.4) U/mg asthmatic group, and (1.46 +/- 0.98) U/mg control group, respectively, the differences being statistically significant between groups. (3) MMP-2 and TIMP-1 mRNA levels in the L-arginine group and the asthmatic group were significantly higher than that in the control group [L-arginine group (0.82 +/- 0.11), (0.51 +/- 0.12); asthmatic group (0.68 +/- 0.14), (0.56 +/- 0.10); control group (0.14 +/- 0.03), (0.11 +/- 0.05), respectively]. The difference in the MMP-2 mRNA levels was significant between the L-arginine group and the asthmatic group (P < 0.05), but the difference in the TIMP-1 mRNA levels between the two groups was not statistically significant. (P > 0.05). (4) A significant positive correlation was found between the MMP-2 mRNA levels and nitrites/nitrates levels in L-arginine group and asthmatic group (r(s) = 0.65, 0.68, P < 0.05), but there was no significant correlation between the nitrites/nitrates levels and the TIMP-1 mRNA levels in the two groups (r(s) = 0.23, 0.18, P > 0.05).
Conclusion:
Nitric oxide may contribute to airway inflammation and remodeling by influencing the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases.
Insights
Nitric oxide influences matrix metalloproteinase and tissue inhibitor of metalloproteinase levels in asthmatic rats, potentially contributing to airway inflammation and remodeling. This study highlights the role of nitric oxide in asthma pathogenesis.
Area of Science:
- Respiratory Medicine
- Molecular Biology
- Biochemistry
Context:
- Asthma is characterized by airway inflammation and remodeling.
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play crucial roles in tissue remodeling.
- Nitric oxide (NO) is implicated in inflammatory processes.
Purpose:
- To investigate the effect of nitric oxide on the expression of MMP-2 and TIMP-1 in a rat model of asthma.
- To analyze the relationship between nitric oxide levels and the expression of MMPs and TIMPs in asthmatic lungs.
Summary:
- Asthmatic rats and rats treated with L-arginine showed significantly higher levels of nitrites/nitrates and nitric oxide synthase (NOS) activity compared to controls.
- Both asthmatic and L-arginine groups exhibited elevated MMP-2 and TIMP-1 mRNA levels, with MMP-2 showing a significant difference between these two groups.
- A positive correlation was observed between MMP-2 mRNA levels and nitrites/nitrates, but not between TIMP-1 mRNA and nitrites/nitrates.
Impact:
- Nitric oxide may exacerbate airway inflammation and remodeling in asthma by altering the MMP/TIMP balance.
- Findings suggest NO as a potential therapeutic target for managing asthma.
- This research provides insights into the molecular mechanisms underlying asthma pathogenesis.