Transforming growth factor-β1‑induced expression of connective tissue growth factor is enhanced in bronchial fibroblasts derived from asthmatic patients

Abstract

Bronchial asthma is accompanied by airway remodeling as well as increased secretion of cytokines, growth factors, and extracellular matrix proteins. Connective tissue growth factor (CTGF) has been suggested to contribute to many fibrotic disorders. However, the ability of human bronchial fibroblasts (HBFs) to express CTGF in response to transforming growth factor-β₁ (TGF‑β₁) has not been studied so far. The aim of the study was to investigate whether HBFs are able to express CTGF when stimulated with TGF‑β₁. All experiments were conducted on in vitro cultures of HBFs isolated from bronchial biopsies obtained from 8 patients with asthma and from 5 nonasthmatic individuals. We performed an analysis of changes in mRNA expression for CTGF and α‑smooth muscle actin and in protein expression for CTGF. We have shown for the first time that HBFs derived from asthmatic patients are capable of higher CTGF expression when stimulated with TGF‑β₁ compared with HBFs isolated from nonasthmatic individuals. Moreover, this effect is significantly reduced after the Wnt signaling pathway activation. Our results point to a pleiotropic effect of TGF-β₁, the elevated levels of which are observed in the bronchoalveolar lavage fluid obtained from asthmatic patients. The structural cells of the bronchi, fibroblasts, stimulated with TGF‑β₁ begin to synthesize CTGF. Moreover, this process can be reversed by the GSK‑3β inhibitor, which activates the Wnt signaling pathway. Our model, based on in vitro primary cell cultures, may be a valuable experimental approach to study the mechanisms underlying bronchial wall remodeling, and in the future it may lead to the development of new therapeutic strategies in asthma.