Functional and phenotypical comparison of myofibroblasts derived from biopsies and bronchoalveolar lavage in mild asthma and sclerodermaReportar como inadecuado




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Respiratory Research

, 7:11

First Online: 23 January 2006Received: 23 August 2005Accepted: 23 January 2006

Abstract

BackgroundActivated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid BALF, are proposed to be important cells in the fibrotic processes of asthma and scleroderma SSc. We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses.

MethodsFibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin α-SMA, ED-A fibronectin, and serine arginine splicing factor 20 SRp20. The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis 2-DE and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry MALDI-TOF-TOF. The Mann-Whitney method was used to calculate statistical significance.

ResultsIncreased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of α-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc.

ConclusionThis study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders.

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Autor: Kristoffer Larsen - Johan Malmström - Marie Wildt - Camilla Dahlqvist - Lennart Hansson - György Marko-Varga - Leif Bjerm

Fuente: https://link.springer.com/



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