کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4211616 | 1280647 | 2010 | 10 صفحه PDF | دانلود رایگان |
SummaryThe reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients’ lung function and airway hyperreactivity (AHR).Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [35S]-sulphate-incorporation/ion chromatography.Patients’ FEV1% predicted and methacholine log PD20 negatively correlated with PICP synthesized by patients’ bronchial fibroblasts (r = −0.74 and r = −0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 ≤ r ≤ 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients’ FEV1% predicted (r = 0.97) and methacholine log PD20 (r = 0.86), whereas negative associations (−0.6 ≤ r ≤ −0.7) were observed for MMP-2 and MMP-3.In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients’ lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients’ lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3.
Journal: Respiratory Medicine - Volume 104, Issue 12, December 2010, Pages 1799–1808