Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma

Respiratory Medicine
Lizbet TodorovaGunilla Westergren-Thorsson

Abstract

The 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 [(35)S]-sulphate-incorporation/ion chromatography. Patients' FEV(1)% predicted and methacholine log PD(20) 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...Continue Reading

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Citations

Jun 25, 2013·Pharmacology & Therapeutics·Audrey H PoonQutayba Hamid
Nov 22, 2011·Molecular Aspects of Medicine·Diego SbardellaMassimo Coletta
Jan 21, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Megan O'ReillyFoula Sozo
Apr 26, 2011·Respiratory Medicine·Lizbet TodorovaAnna Miller-Larsson

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